Veterinary Neurobiology.pdf

8/14/2019 Veterinary Neurobiology.pdf

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CONTENTS

1: Neurohistology I: Cellular Features .......................3

2: Neurohistology II: Meninges/Receptors ...............11

3: Nervous System Development (Embryology) ......18

4: Spinal Cord Organization .....................................31

5: Spinal Reflexes & Neuronal Integration ..............36

6: Cranial Nerves ........................................................44

7: Vestibular System ...................................................50

8: Posture and Movement ..........................................55

9: Cerebral Hemisphere and Cortex .........................60

10: Nociception I ...........................................................65

11: Nociception II .........................................................71

12: Cerebellum ..............................................................76

13: Diencephalon and Hypothalamus .........................81

14: Olfaction and Limbic System ................................86

15: Auditory System .....................................................90

16: Visual System ..........................................................96

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Lecture 1

Neurohistology I:

Cells and General FeaturesOverall Objectives:to understand the histological components of nervous tissue;

to recognize the morphological features of neurons; andto differentiate myelinated from non-myelinated axons

I. Basic Organization:A. Central Nervous System(CNS)brain and spinal cord

B. Peripheral Nervous System(PNS)all cranial and spinal nerves and their associated

roots and ganglia

Functional PNS Divisions:

A. Somatic Nervous Systema one neuron system that innervates (voluntary)

skeletal muscle or somatosensory receptors of the skin, muscle & joints.

B. Autonomic Nervous Systema two neuron visceral efferent system that

innervates cardiac and smooth muscle and glands. It is involuntary

and has two major subdivisions:

1) Sympathetic (thoracolumbar)

2) Parasympathetic (craniosacral)

II. Histological Components:

A.Supporting (non-neuronal) CellsGlial cells provide support and protection forneurons and outnumber neurons 10:1. The CNS has three types and the PNS has one:

1. Astrocytesstar-shaped cells that play an active role in brain function by influencing the

activity of neurons. They are critical for 1) recycling neurotransmitters; 2) secreting

neurotrophic factors (e.g., neural growth factor) that stimulate the growth and mainte-

nance of neurons; 3) dictating the number of synapses formed on neuronal surfaces and

modulating synapses in adult brain; and 4) maintaining the appropriate ionic composition

of extracellular fluid surrounding neurons, by absorbing excess potassium and other

larger molecules.

2. Oligodendrocytes The oligodendrocyte is the analog of the Schwann cell in the central

nervous system and is responsible for forming myelin sheaths around brain and spinal

cord axons. Myelin is an electrical insulator.

3. Microgliaare the smallest of glial cells. They represent the intrinsic immune effector

cells of the CNS and underlie the inflammation response that occurs following damage to

the central nervous system and the invasion of microorganisms.

4. Lemmocytes (Schwann Cells) Schwann cells are glia cells of the PNS. They wrap

individually around the shaft of peripheral axons, forming a layer or myelin sheath along

segments of the axon. The Schwann cell membrane, which forms the myelin sheath, is

composed primarily of lipids; the lipid serves as an insulator thereby speeding the trans-

mission rate of action potentials along the axon.


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dendritic zone(receives input)

axon(conducts excitation)

telodendriticzone

myelinnode

myelininternode

telodendritic branches(with terminal bulbs)

next neuron (dendrite)

axon hillock(of cell body)

input (telodendrite) dendrite

cell body (soma)

initial segment (of axon)

axon

Multipolar Neuron

5. Ependyma in addition to the above glial cells, the CNS has epithelial-like cells that line

the ventricles of the brain and the central canal of the spinal cord.

Note:Glial cells are capable of reproduction, and when control over this capacity is lost

primary brain tumors result. Astrocytomas and glioblastomas are amongst the

most deadly or malignant forms of cancer.

B. Neurons(nerve cells)neurons are the structural and functional units of the nervous system; they are specialized to conduct electrical signals.

Note:The plasma membrane of the neuron contains both voltage gated ion channels (in-

volved in generation and conduction of electrical signals) and receptors (which bind neu-

rotransmitters and hormones and use distinct molecular mechanisms for transmembrane

signaling; examples include ligand-gated ion channels and G protein coupled receptors).

1. Morphological Features of neurons(3 component parts; see Fig.1 below):

A. Cell body the expanded portion of the neuron that contains the nucleus;

stains basophilically due to the abundance of RER and polyribosomes;

the clumps of RER & polyribosomes are referred to as Nissl Bodies.

B.Dendrites one to many extensions of the cell body;

specialized to receive input from other neurons or from receptors;

contain Nissl bodies in their proximal parts and thus the initial portions

of dendrites stain basophilically;

often have small protrusions, called dendritic spines, that expand thedendritic surface area and serve as sites of synaptic contact.

Figure 1: Diagram of a neuron illustrating its component parts

axon terminal branches(transmit neuronal output)

(axon terminal)


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C. Axon typically one per neuron;

an extension of the cell body that is specialized for conducting electrical

impulses(action potentials).

lacks Nissl bodies and does not stain with routine histological stains.

Note:Axons are either myelinated(surrounded by a fatty insulating sheath that speeds

conduction of the electrical impulse) or non-myelinated(lacking a myelin sheath and

thus conduct impulses slowly).

2. Definitions:

A. Ganglion a collection of neuron cell

bodies situated in the PNS

B. Nucleus this term is used in a special

sense in neurobiology to describe a collection of

neuronal cell bodies in the CNS (accumulation of

gray matter)

C. Nerves bundles of axons that extend

out from the brain as cranial nerves and from the

spinal cord as spinal nerves (surrounded by connec-

tive tissue sheaths)

D. Tract a bundle of axons (nerve fibers)

within the CNS (connective tissue is absent)

3. Neuronal Classification:

A.Anatomically,by number of processes:

1) Unipolar (pseudounipolar)

Neuron has one process that bifurcates; the cell

body of this neuronal type is found in spinal and

cranial ganglia.

2) Bipolar Neuron has 2 pro-

cesses (relatively rare; retina of eye and certain

cranial ganglia).

3) Multipolar Neuron many

processes; typically 1 axon and 2 or more dendrites

(most common type of neuron).

B. Functionally:1)Motor (Efferent) related to innervation of muscle, glands etc.; activation of

these neurons leads to some motor event (i.e., contraction of a muscle).

2) Sensory (Afferent) related to the transfer of sensory information (i.e., pain,

touch, pressure, etc.); e.g., neurons of spinal (dorsal root) ganglia.

3) Interneurons neither motor or sensory (e.g., neurons responsible for the various

spinal reflexes).

MultipolarNeuron

UnipolarNeuron

BipolarNeuro

telodendria(synapse in CNS)

coiled proximalaxon

cell body

cell body

axon hillock(of cell body)

dendrite

axon

cell bodyaxon

dendritic zone(synapses onhair cells ofcochlea)

receptor(free nerveendings)

telodendria

Types of Neurons


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4. Axons:

Axons are neuron processes that project to and synapse with dendrites or cell bodies of other

neurons or with non-neuronal targets (e.g. muscle). Swellings, termed axonal varicosities/boutons,

are foundalong the axon or at its terminal branches and are typically the sites where synapses occur

(see Neurohistology, Lecture II). Morphologically axons are divided into two types: myelinated and

non-myelinated.

A. MYELINATED AXONS (>1 m; fast conducting):Myelinatedaxons are invested with a membranous, lipid sheath (making them the

largest and fastest conducting nerve fibers). Myelin is a highly organized multilamellar structure

formed by the plasma membrane of oligodendrocytes in the CNS and lemmocytes (Schwann cells)

in the PNS. Myelin is an electrical insulator which allows increased speed of conduction along an

axon. Myelinated axons located in the PNS differ from those in the CNS both in chemical composi-

tion and in the cell type that produces the myelin.

1)Light microscopic appearance:Under the light microscope, the myelin sheath appears as a tube surrounding the

axon. In H & E or Triple-stained sections, myelin appears like spokes of a wheel around the axon;this appearance is actually artifactual in that tissue processing (dehydration in alcohols and clearing

in xylene) dissolves lipid components of the myelin leaving nonlipid components. This remaining

protein configuration is called neurokeratin.

2)Nodes of Ranvier:The nodes are breaks in the continuity of the myelin sheath which occur regularly in

both the peripheral and central nervous systems. They represent the intervals between adjacent

segments of myelin and occur at the junction of two lemmocytes in the PNS or two oligodendrocytes

in the CNS. The nodes appear as constrictions along the nerve fiber.

Fig. 3. Peripheral nerve tissue (light microscopy).

Top. Longitudinal illustration of a myelinated

axon (myelin is gray; cytoplasm is black).

Lemmocytes form myelin sheaths around one

axon. Adjacent lemmocytes (myelin sheaths) are

separated by nodes. Cytoplasm filled clefts are

sometimes evident in myelin sheaths.

Right. Myelin sheaths appear as individual black

rings in a transverse section through a nervefascicle.


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AB

C

DE

mesaxon

NN

N

a

a

a

a

a

myelinsheath

neurolemmocyte

nonmyelinated axon

Myelin Development (PNS)

Figure 6: Diagrams showing features of myelinated and non-myelinated

nerve fiber development.

4) CNS:

The myelin sheath is produced by oligodendrocytes (one of the CNS glial cells). Asingle oligodendrocytes will provide myelin for multiple axons. CNS myelin has more

glycolipid and less phospholipid than PNS myelin. In the CNS, myelinated axons lack a

basal lamina and endoneurium.


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Clinical Correlation

Demyelination- Demyelination is the destructive removal of

myelin, an insulating and protective fatty protein that sheaths nerve cell

axons. When axons become demyelinated, they transmit the nerve im-

pulses 10 times slower than normal myelinated ones and in some cases

they stop transmitting action potentials altogether. There are a number ofclinical diseases associated with the breakdown and destruction of the

myelin sheath surrounding brain, spinal cord or peripheral nerve axons.

Degenerative myelopathy, for instance, is a progressive disease of

the spinal cord in older dogs. The breeds most commonly affected include

German Shepherds, Welsh Corgis, Irish Setters and Chesapeake Bay

Retrievers. The disease begins in the thoracic area of the spinal cord and

is associated with degeneration of the myelin sheaths of axons that com-

prise the spinal cord white matter. The affected dog will wobble when

walking, knuckle over or drag their feet, and may cross their feet. As thedisease progresses, the limbs become weak and the dog begins to buckle at

the knees and have difficulty standing. The weakness gets progressively

worse until the dog is unable to walk.

Note:

Unlike the PNS, axons in the CNS do not regenerate following

injury. In part, this is due to the fact that CNS myelin contains several

proteins that inhibit axonal regeneraltion.

B. NON-MYELINATED AXONS (< 1 m; slow conducting):

1) PNS Non-myelinated axons are embedded in infoldings of the plasma membrane of achain of lemmocytes. Each lemmocyte typically encloses 5-20 axons (see Fig. 5, previous page).

Axoplasm clumps and stains poorly with routine histological stains. A group of axons and associ-

ated lemmocytes are surrounded by basal lamina and endoneurium.

2) CNS Nonmyelinated axons are notassociated with oligodendrocytes but run freewithout any type of ensheathment. They are separated from one another by astrocytic processes.


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Lecture 2

Neurohistology II:

Synapses, Meninges, & Receptors

Overall Objectives:To understand the concept of the synapse; to understand the concept of

axonal transport; to learn to identify the three layers of the meninges; and to understand

how receptors are classified.

I. The Synapse:The synapse is a specialized point of functional contact between neurons or between a neuron and

a target organ (i.e., muscle) that allows neurons to communicate with one another or with their target

cells.

Synaptic Anatomy . . .

The synpase is a site of apposi-

tion between a presynaptic element ofone neuron and a postsynaptic mem-

brane of a target neuron (or an effector

organ); where, typically, a presynaptic

axon enlargement releases transmitter

molecules that diffuse across a synap-

tic cleft and bind to receptor channels

in the postsynaptic membrane.

Synapses are comprised of three

elements:

a) Presynaptic nerve terminal

contains synaptic vesicles

which house a chemical

neurotransmitter that is re-

leased after vesicle fusion with

the presynaptic terminal

plasma membrane.

b) Postsynaptic element a

dendrite, a cell body, or a

target cell receiving the synap-tic input. Receptor protein

molecules, to which neu-

rotransmitter molecules bind,

are embedded in the postsyn-

aptic plasma membane.

c) Synaptic Cleft a gap between pre- and post-synaptic elements into which neurotransmitter

molecules are released.


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Synaptic Physiology . . .

Presynaptic events:

Neurotransmitter molecules are released in proportion to the amount of Ca++influx, in turn

proportional to the amount of presynaptic membrane depolarization, i.e.,

in the resting state, the presynaptic membrane is polarized

when an action potential arrives at the end of the axon, the adjacent presynaptic

membrane is passively depolarized (toward zero transmembrane potential) voltage-gated Ca++channels allow Ca++influx (driven by [Ca++] gradient).

elevated [Ca++] triggers vesicle mobilization and docking with the plasma membrane

a number of vesicles fuse with presynaptic plasma membrane and release

neurotransmitter molecules (about 5,000 per vesicle)by exocytosis.

transmitter molecules diffuse across the cleft & bind with postsynaptic receptor proteins

neurotransmitter molecules are eliminated from synaptic clefts via pinocytotic uptake by

presynaptic or glial processes and/or via enzymatic degradation at the postsynaptic

membrane. The molecules are recycled.

subsequently, presynaptic plasma membrane repolarizes (due to K+channel conductance).

Postsynaptic events:

Neurotransmitter binding results in a proportional ion flux across the postsynaptic membrane.

The particular excitability effect depends on the nature of the ion flux which depends on the nature

of the ion channels in the particular postsynaptic membrane, i.e.,

in the resting state, postsynaptic plasma membrane is polarized

(voltage activated K+channels dominate conductance)

arriving neurotransmitter molecules bind briefly/repeatedly to ligand-gated receptors, which

opens ion channels directly or by means of second messengersactivation of [Na+ & K+] channels > leads to depolarization toward zero potential;

activation of Cl- or K+channels > hyperpolarization of postsynaptic membrane.

a postsynaptic potential (PSP) results from the altered membrane conductanceEPSP = Excitatory PSP = depolarization toward zero potential, excites the

postsynaptic cell

IPSP = Inhibitory PSP = hyperpolarization (serves to cancel EPSPs), inhibits the

postsynaptic cell

following the removal/degradation of

neurotransmitter molecules, the

postsynaptic membrane is

re-polarized (K+channel conductance

again dominates.)

Note: PSPs constitute electrotonic conduc-tion, a passive voltage spread (in contrast to

the regenerative conduction of which axons

are capable). PSPs decay exponentially, over

distance and with time. The magnitude of a

PSP depends on the number of open ion

channels which, in turn, depends on the

amount of neurotransmitter released.

0

-70

mV

Distance

T

i

m

e

Electrotonic Conduction

EPSP

-70

-70

-70


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Additional Comments

synaptic transmission is unidirectional (vesicles are located on only one side).

glutamate is the major excitatory neurotransmitter in the nervous system; GABA and glycine are the major

inhibitory neurotransmitters.

synaptic transmission is slower than axonal conduction; each synapse introduces delay into a neural

pathway (at least 0.5 msec/synapse). synapses are more susceptible to fatigue, hypoxia, and drug effects than are axons (generally pathways

fail first at synapses).

different kinds of drugs (tranquilizers, anesthetics, narcotics, anticonvulsants, muscle relaxants, etc.)

work by modifying activity selectively among the different kinds of chemical synapses.

certain diseases are manifestations of selective synaptic dysfunction; e.g., Parkinson's disease, tetanus,

myasthenia gravis, various intoxications, etc.

II. Connective Tissue Coverings of Axons in the PNS:1. Endoneurium-- surrounds each myelinated axon, or a group of nonmyelinated axons.

2. Perineurium surrounds each nerve fascicle (a bundle of axons); consists of a perineural

epitheliumand associated collagenous connective tissue. The perineurium participates in forming a

blood-nerve barrier which limits the passage of water-soluble substances and proteins from blood

into the endoneurial compartment. (The integrity of this barrier is altered in certain neuropathies

and following nerve trauma.)

3. Epineurium surrounds the entire nerve


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III. Axonal Transport:1. The net movement of substances along the axon; 2 rates:

A. Fast Axonal Transport100-500 mm/day

B. Slow Axonal Transport1-10 mm/day

2.Anterograde Transporttransport of materials down the axon away from the cell body;important for renewing proteins along the axon and thus maintaining the axon.

3.Retrograde Transporttransport from the axon terminal toward the cell body; important

mechanism by which virus particles (rabies) and neurotoxins (tetanus toxin) gain access to the CNS.

[Note: Tetanus and Botulinum toxins are proteases which cleave neuronal SNARE-proteins.]

IV. Meninges:protective connective tissue sheaths surrounding the brain and spinal cord. There are three layers of meninges:

1. Dura Mater the outermost layer consisting of coarse, irregular connective tissue;

composed of collagen and elastic fibers.

2. Arachnoid middle layer of

the meninges; it consists of a distinct

membrane and numerous fibrous trabecu-

lae on its inner surface. This trabecular

network forms the structural framework for

the subarachnoid space which lies between

the arachnoid proper and the underlying

pia mater.

The subarachnoid spacecontains cerebrospinal fluid (CSF). At

certain points the subarachnoid space is

dilated and forms cisterns. The cisterna

magnaand lumbar cisterns are important

clinically because that is where CSF taps

are performed.

[Note:CSF is a clear colorless

fluid that surrounds and permeates the

entire central nervous system. It functions

to protect, support and nourish the CNS.]

3. Pia Mater(from the latin term meaningtender mother), the innermost layer of the

meninges, it forms a thin protective membrane which adheres to the surface of the brain and spinal

cord. It consists of flattened fibrocytes superficial to elastic and collagen fine fibers that extends into

the numerous depressions and fissures on the surface of the brain and cord. It is very vascular.


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V. Receptors:

1. Receptor= a specialized region located on a peripheral terminal branch of an axon of a

primary afferent neuron, that can serve as a transducerconverting environmental

energy (sensory stimuli) into depolarizing ionic current (nerve signals). The number of

receptors per neuron ranges from several (small receptive field) to several dozen (large

receptive field).

vs.

Sense organ = an organized collection of receptor cells, with which the dendritic zones of afferent neurons

synapse. The excitability of receptor cells is modified by environmental energy, i.e., the receptor cells act

as transducers.Sense organs are: retina, cochlea,

vestibular apparatus, taste buds, and

olfactory epithelium. Neurons that synapse on

receptor cells are SSAor SVAin type and commonly bipolar rather than unipolar.

2. Classification of receptor populations:

Receptor classification based onMorphology:

1) free nerve endingsterminal branches ramifying among epithelial cells, very

common especially in the skin (mediate pain sensation, itch thermal sensations).

2) tactile discsconsists of a terminal expansions of an afferent axon which are

joined to modified epidermal cells (found in skin and mucous membranes).3) encapsulatedeach receptor is encapsulated by lemmocytes and perineural

epithelium (examples: pacinian corpuscles, tactile corpuscles, muscle spindles).

Receptor classification based onLocation:

Falx cerebri

Arachnoid villus

Dura mater

Arachnoid

Subarachnoid space

Arachnoidtrabecula

White matter

Cerebralcortex

Pia mater

Dorsal sagittal venous sinus

Cranial Meninges

3)1) 2)


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1) Exteroceptorsassociated with skin and subcutaneous tissue (GSA)

2) Proprioceptorsassociated with muscles, tendons and joints (GSA)

3) Interoceptorslocated in viscera (GVA)

Receptor and sense organ classification based onModality(energy sensitivity):

1) mechanoreceptorsdetect mechanical deformation (touch, pressure, vibration)

2) thermoreceptorsdetect changes in temperature (some detect warmth, some detect cold)

3) nociceptorsdetect damage to tissue (pain receptors); also detect itch

4) electromagneticdetect light on the retina of the eye

5) chemoreceptorsdetect chemical molecules, including: taste receptors, olfactory

receptors, arterial oxygen receptors in the aortic arch and carotid bodies, blood

osmolarity in the hypothalamus and blood glucose and fatty acid receptors in the

hypothalamus.

Schematic diagram illustrat-

ing various types of periph-

eral receptors:


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Central Nervous System

Formation of neurons and glial cells from neuroepithelium:

Neuroepithelium gives rise to neurons, glial cells (astrocytes

and oligodendrocytes), and ependymal cells (additionally, the CNS contains

blood vessels and microglial cells derived from mesoderm).

Neuroepithelial cells have processes which contact the inner and outer

surfaces of the neural tube; they undergo mitotic division in the following manner: the nucleus (and perikaryon) moves away from the neural cavity for

interphase (DNA synthesis);

the nucleus moves toward the neural cavity and the cell becomes

spherical and looses its connection to the outer surface of the neural tube for mito-

sis; this inward-outward nuclear movement is repeated at each cell division.

Some cell divisions are differential, producing neuroblasts

which give rise to neurons or glioblasts (spongioblasts) which give

rise to glial cells (oligodendrogliocytes and astrocytes). Neuroblasts and

glioblasts lose contact with surfaces of the neural tube and migrate

toward the center of the neural tubewall.

Note: Microglial are derived from mesoderm associated withinvading blood vessels.

Layers and plates of the neural tube:

Accumulated neuroblasts and glioblasts form the mantle

layer, a zone of high cell density in the wall of the nerual tube. Cells

that remain lining the neural cavity are designated ependymal cells;

they form an ependymal layer. Surrounding the mantle layer, a cell-

sparse zone where axons of neurons and some glial cells are present

is designated the marginal layer. The mantle layer becomes gray mat-

ter and the marginal layer becomes white matter of the CNS.

The lateral wall of the neural tube is divided

into two regions (plates). A bilateral indentation evi-

dent in the neural cavity (the sulcus limitans) servesas a landmark to divide each lateral wall into an alar

plate(dorsal) and a basal plate(ventral). Midline re-

gions dorsal and ventral to the neural cavity constitute,

respectively, the roof plateand theoor plate.

The basal plate contains efferent neu-

rons that send axons into the PNS.

The alar plate contains neurons that

receive input from the PNS.


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Formation of the Central Nervous System

The cranial end of the

neural tube forms three vesicles

(enlargements) that further di-

vide into the ve primary divi-

sions of the brain. Caudal to thebrain the neural tube develops

into spinal cord.

Flexures: During devel-

opment, the brain undergoes three

exures which generally disappear

(straighten out) in domestic animals.

The midbrain exureoccurs

at the level of the midbrain.

The cervical exureappears

at the junction between the brain and

spinal cord (it persists slightly in do-

mestic animals).

Thepontine exureis con-

cave dorsally (the other exures are

concave ventrally).

Adult CNS Structures Derived From Embyonic Brain Divisions

Note:The portion of brain remaining after the cerebrum and cerebellum are removed is referred to as the brain stem.

Embryonic Derived Denitive Associated

Brain Division Brain Structures Brain Cavities Cranial Nerves

FOREBRAIN Telencephalon Cerebrum Lateral ventricles Olfactory (I)

Diencephalon Thalamus; Third Ventricle Optic (II)

hypothalamus; etc.

MIDBRAIN

Mesencephalon Midbrain Mesencephalic aqueduct III & IV

HINDBRAIN

Metencephalon Pons and Cerebellum V

Fourth ventricle

Myelencephalon Medulla Oblongata VIXII


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Spinal cord development the neural cavity becomes central canallined

by ependymal cells;

growth of alar and basal plates, but not roof

and oor plates, results in symmetrical right and left

halves separated by a ventral median ssure and a dor-

sal median ssure (or septum); the mantle layer develops into gray matter,i.e., dorsal and ventral gray columnsseparated by intermediate gray matter (in prole, the columns are usually called

horns); cell migration from the basal plate produces a lateral gray column (horn) at thoracic and cranial lumbar levels of

the spinal cord (sympathetic preganglionic neurons);

the marginal layer becomes white matter(which is subdivided bilaterally into a dorsal funiculus

(bundle), a lateral funiculus, and a ventral funiculus ).

Enlargements of spinal cord segments that innervate limbs (cervical and lumbo-

sacral enlargements) are the result of greater numbers of neurons in those segments,

due to less neuronal degeneration compared to segments that do not innervate limbs.

Hindbrain:Medulla oblongata and pons

alar plates move laterally and the cavity of the neural tube expands dorsally forming a

fourth ventricle; the roof of the fourth ventricle (roof plate)is stretched and reduced to a layer of ependymal cells covered

by pia mater; achoroid plexus develops bilaterally in the roof of

the ventricle and secretes cerebrospinal uid;

the basal plate (containing efferent neurons

of cranial nerves) is positioned medial to the alar

plate and ventral to the fourth ventricle;

white and gray matter (marginal & mantle

layers) become intermixed (unlike spinal cord); cer-

ebellar development adds extra structures.

Hindbrain:Cerebellum

NOTE: Adult cerebellum features surface gray matter, called cerebellar cortex, and three pair of

cerebellar nucleilocated deep within the cerebellar white matter. The cerebellum connects to

the brain stem by means of three pair of cerebellar peduncles, each composed of white matterbers.

Cerebellar cortex is composed of three layers: a supercial molecular layerwhich is rela-

tively acellular; a middlepiriform(Purkinje) cell layerconsisting of a row of large cell bodies;

and a deep granular (granule cell)layercomposed of numerous very small neurons.

The cerebellum functions to adjust muscle tone and coordinate posture and movement so

they are smooth and uid vs. jerky and disunited.

bilateral rhombic lipsare the rst evidence of cerebellar development; the lips are expan-

sions of the alar plate into the roof plate;the rhombic lips merge medially, forming a midline isthmus(the lipsform the two cerebellar hemispheres and the isthmus forms the vermis of the cerebellum);


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cellular migrations:

supercial and deep layers of neu-

rons are evident within the mantle layer of the future

cerebellum; the deep cells migrate (pass the super-

cial cells) toward the cerebellar surface and become

Purkinje cells of the cerebellar cortex; meanwhile,

neurons of the supercial layer migrate deeply and

become cerebellar nuclei;

neuroblasts located laterally in the

rhombic lip migrate along the outer surface of the

cerebellum, forming an external germinal layer(which continues to undergo mitosis); subsequently,

neurons migrate deep to the Purkinje cells and form the granule cell layer of the cerebellar cortex; some alar plate neurons migrate to the ventral surface of the pons, forming pontine nuclei which send

axons to the cerebellum.

Migration of neuron populations past one another allows connections to be estab-

lished between neurons of the respective populations. Neurons that fail to connect aredestined to degenerate. Connections are made by axons that subsequently elongate as

neurons migrate during growth.

Midbrain the neural cavity of the midbrain becomes mesencephalic aqueduct(which is not a ventriclebecause it is completely surrounded by brain tissue and thus it lacks a choroid

plexus).

alar plates form two pairs of dorsal bulges which

become rostral and caudal colliculi(associated with visual and auditoryreexes, respectively);

the basal plate gives rise to oculomotor (III) and troch-

lear (IV) nerves which innervate muscles that move the eyes.

Note:The midbrain is the rostral extent of the basal plate (efferent neurons).

Forebrain (derived entirely from alar plate)

Diencephalon:

the neural cavity expands

dorsoventrally and becomes the

narrow third ventricle, the roof plateis stretched and choroid plexuses develop

bilaterally in the roof of the third ventricle

and secrete cerebrospinal uid;

the oor of the third

ventricle gives rise to the neurohyp-

ophysis (neural lobe of the pituitary

gland);


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the mantle layer of the diencephalon gives rise to thalamus, hypothalamus, etc.; the thal-

amus enlarges to the point where right and left sides meet at the midline and obliterate the center of the third ventricle.

the optic nerve develops from an outgrowth of the wall of the diencephalon.

Telencephalon (cerebrum):

bilateral hollow outgrowths become right and left cerebral hemispheres; the cavity of each

outgrowth forms a lateral ventriclethat communicates with the third ventricle via an interventricular

foramen (in the wall of each lateral ventricle, a choroid plexus develops that is continuous with a choroid plexus of the

third ventricle via an interventricular foramen);

at the midline, the rostral end of the telencephalon forms the rostral wall of the third ven-

tricle (the wall is designated lamina terminalis);

the mantle layer surrounding the lateral ventricle in each hemisphere gives rise to basal

nuclei and cerebral cortex;

cellular migrations that form cerebral cortex:

from the mantle layer, cells migrate radially to the surface of the cerebral hemi-sphere, guided by glial cells that extend from the ventricular surface to the outer surface of the cere-

bral wall (thus each locus of mantle gives rise to a specic area of cerebral cortex);

migration occurs in waves; the rst wave (which becomes the deepest layer of

cortex) migrates to the surface of the cortex; the second wave (which forms the next deepest layer of

cortex) migrates to the cortical surface, passing through rst wave neurons which are displaced to a

deeper position; the third wave . . . etc. (the cerebral cortex has six layers.

Cell connections are established within the cerebral cortex as waves of newly

arriving neurons migrate through populations of neurons that arrived earlier.

NOTE: Carnivores are born with a nervous system that does not mature until about six weeks

postnatally (mature behavior is correspondingly delayed). In herbivores, the nervous

system is close to being mature at birth.


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Peripheral Nervous System

NOTE: The peripheral nervous system (PNS) consists of cranial and spinal nerves. Nerve bers

within peripheral nerves may be classied as afferent (sensory) or efferent (motor) and

as somatic (innervating skin and skeletal muscle) or visceral (innervating vessels and

viscera). The visceral efferent (autonomic) pathway involves two neurons: 1] a pregan-

glionic neuron that originates in the CNS and 2] a postganglionic neuron located entirely

in the PNS. The glial cell of the PNS is the neurolemmocyte (Schwann cell). All afferent neurons are unipolar and have their cell bodies in sensory ganglia, either

spinal ganglia on dorsal roots or ganglia associated with cranial nerves. Somatic efferent

and preganglionic visceral efferent neurons have their cell bodies located in the CNS, but

their axons extend into the PNS. Postganglionic visceral efferent neurons have their cell

bodies in autonomic ganglia.

neurolemmocytes(Schwann cells) arise from neural crestand migrate throughout the

PNS, ensheathing and myelinating axons and forming satellite cells in ganglia;

afferent neuronsorig-

inate from neural crest as bipolar

cells that subsequently become uni-

polar; in the case of cranial nerves,

afferent neurons also originate

from placodes (placode = localized

thickening of ectoderm in the head);

postganglionic visceral

efferent neuronsarise from neural

crest, the cells migrate to form au-

tonomic ganglia at positions within

the head, or beside vertebrae (alongsympathetic trunk), or near the

aorta, or in the gut wall (the latter areparasympathetic and come from sacral and

hindbrain regions);

somatic efferent neurons

andpreganglionic visceral efferent neuronsarise from the basal plate of the neural tube; their cell

bodies remain in the CNS and their axons join peripheral nerves;

Peripheral nerves establish contact early with the nearest somite, somitomere,

placode, or branchial arch and innervate derivatives of these embryonic structures.

Innervation continuity is retained even when the derivatives are considerably displaced

or when other structures have obstructed the pathway. The early establishment of an innervation

connection explains why some nerves travel extended distances and make detours to reach distant

inaccessible targets. The foremost example is the recurrent laryngeal nerve which courses from the brainstem to thelarynx via the thorax, because the heart migrates from the neck to the thorax pulling the nerve with it.


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Note:Cranial nerves innervate specic branchial arches and their derivatives:

trigeminal (V) - innervates rst branchial arch (muscles of mastication)

facial (VII) - innervates second branchial arch (muscles of facial expression)

glossopharyngeal (IX) - innervates third branchial arch (pharyngeal muscles)

vagus (X) - 4 & 6 branchial arches (muscles of pharynx, larynx, & esophagus)

Formation of Meninges

Meninges surround the CNS and the roots of spinal and cranial nerves.

Three meningeal layers (dura mater, arachnoid, and pia mater) are formed as follows:

mesenchyme surrounding the neural tube aggregates into two layers;

the outer layer forms dura mater;

cavities develop and coalesce within the inner layer, dividing it into arachnoid and pia

mater; the cavity becomes the subarachnoid space which contains cerebrospinal uid.


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Special Senses

Formation of the Eye Both eyes are derived from a single eld of the neural plate. The single eld separates into

bilateral elds associated with the diencephalon. The following events produce each eye:

a lateral diverticulum from the diencephalon forms an optic vesicleattached to the dien-

cephalon by an optic stalk;

a lens placodedevelops in the surface ectoderm where it is contacted by the optic vesicle;

the lens placode induces the optic vesicle to invaginate and form an optic cupwhile the placode

invaginates to form a lens vesiclethat invades the concavity of the optic cup;

an optic ssureis formed by invagination of the ventral surface of the optic cup and optic

stalk, and a hyaloid arteryinvades the ssure to reach the lens vesicle;

NOTE: The optic cup forms the retinaand contributes to formation of the ciliary

body and iris. The outer wall of the cup forms the outer pigmented layer

of the retina, and the inner wall forms neural layers of the retina.

The optic stalk becomes the optic nerveas it lls with axons traveling

from the retina to the brain.

The lens vesicle develops into the lens, consisting of layers of lens

bers enclosed within an elastic capsule.

The vitreous compartment develops from the concavity of the optic

cup, and the vitreous bodyis formed from ectomesenchyme that enters the

compartment through the optic ssure.


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ectomesenchyme (from neural crest) surrounding the optic cup condenses to form inner

and outer layers, the future choroidand sclera, respectively;

the ciliary bodyis formed by thickening of choroid ectomesenchyme plus two layers of

epithelium derived from the underlying optic cup; the ectomesenchyme forms ciliary muscle and the collage-

nous zonular bers that connect the ciliary body to the lens;

the irisis formed by

choroid ectomesenchyme plus the

supercial edge of the optic cup; the

outer layer of the cup forms dilator

and constrictor muscles and the inner

layer forms pigmented epithelium;

the ectomesenchyme of the iris forms

apupillarymembranethat conveys

an anterior blood supply to the de-

veloping lens; when the membrane

degenerates following development

of the lens, a pupil is formed;

the corneadevelops fromtwo sources: the layer of ectomesen-

chyme that forms sclera is induced

by the lens to become inner epithe-

lium and stroma of the cornea, while

surface ectoderm forms the outer

epithelium of the cornea; the anteri-

or chamber of the eye develops as a

cleft in the ectomesenchyme situated

between the cornea and the lens;

the eyelidsare formed by upper and lower folds of ectoderm, each fold includes a mesen-

chyme core; the folds adhere to one another but they ultimately separate either prenatally (ungulates)

or approximately two weeks postnatally (carnivores); ectoderm lining the inner surfaces of the folds

becomes conjunctiva, and lacrimal glandsdevelop by budding of conjunctival ectoderm;

skeletal muscles that move the eye (extraocular eye mm.)are derived from rostral somito-

meres (innervated by cranial nerves III, IV, and VI).

Clinical considerations:

The ungulate retina is mature at birth, but the carnivore retina does not fully mature until about 5

weeks postnatally.

Retinal detachment occurs between the neural and outer pigmented layers of the retina (inner

and outer walls of the optic cup) which do not fuse but are held apposed by pressure of the vitre-

ous body. Coloboma is a defect due to failure of the optic ssure to close.

Microphthalmia (small eye) results from failure of the vitreous body to exert sufcient pressure

for growth, often because a coloboma allowed vitreous material to escape.

Persistent pupillary membrane results when the pupillary membrane fails to degenerate and

produce a pupil.


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Formation of the Ear The ear has three components: external ear, middle ear, and inner ear. The inner ear contains

sense organs for hearing (cochlea) and detecting head acceleration (vestibular apparatus), the latter

is important in balance. Innervation is from the cochlear and vestibular divisions of the VIII cranial nerve. The

middle earcontains bones (ossicles) that convey vibrations from the tympanic membrane (ear drum)

to the inner ear. The outer earchannels sound waves to the tympanic membrane.

Inner ear:

an otic placodedevelops in surface ectoderm adjacent to the hindbrain; the placode in-

vaginates to form a cup which then closes and separates from the ectoderm, forming an otic vesicle

(otocyst); an otic capsule, composed of cartilage, surrounds the otocyst; some cells of the placode and vesicle become neuroblasts and form afferent neurons of the vestibulocochlear

nerve (VIII);

the otic vesicle undergoes differential growth to form the cochlear duct and semicircular

ducts of the membranous labyrinth; some cells of the labyrinth become specialized receptor cells found in macu-

lae and ampullae;

the cartilagenous otic capsule undergoes similar differential growth to form the osseous

labyrinth within the future petrous part of the temporal bone.


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Middle ear:

the dorsal part of therst pharyngeal pouch

forms the lining of the auditory tube and tympanic cavity(in the horse a dilation of the auditory tube develops into the guttural

pouch);

the malleus and incus develop as endochondral

bones from ectomesenchyme in the rst branchial arch and

the stapes develops similarly from the second arch (in sh,these three bones have different names; they are larger and function as

jaw bones).

Outer ear:

the tympanic membrane is formed by appo-

sition of endoderm and ectoderm where the rst pharyn-

geal pouch is apposed to the groove between the rst and

second branchial arches;

the external ear canal (meatus) is formed by the groove between the rst and second bran-

chial arches; the arches expand laterally to form the wall of the canal and the auricle (pinna) of theexternal ear.

Taste buds Taste buds are groups of specialized (chemoreceptive) epithelial cells localized principally on

papillae of the tongue. Afferent innervation is necessary to induce taste bud formation and maintain

taste buds. Cranial nerves VII (rostral two-thirds of tongue) and IX (caudal third of tongue) innervate the taste buds of

the tongue.

Olfaction Olfaction (smell) involves olfactory mucosa located caudally in the nasal cavity and the

vomeronasal organ located rostrally on the oor of the nasal cavity. Olfactory neurons are chemore-

ceptive; their axons form olfactory nerves (I).

an olfactory (nasal) placode appears bilaterally as an ectodermal thickening at the rostral

end of the future upper jaw; the placode invaginates to form a nasal pit that develops into a nasal

cavity as the surrounding tissue grows outward; in the caudal part of the cavity, some epithelial cells

differentiate into olfactory neurons;

the vomeronasal organ develops as an outgrowth of nasal epithelium that forms a blind

tube; some epithelial cells of the tube differentiate into chemoreceptive neurons.


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Lecture 4

Spinal Cord Organization

The spinal cord . . .

connects with spinal nerves, through afferent

& efferent axons in spinal roots;

communicates with the brain, by means of

ascending and descending pathways that

form tracts in spinal white matter; and

gives rise to spinal reflexes, pre-determined

by interneuronal circuits.

Gross anatomy of the spinal cord:The spinal cord is a cylinder of CNS. The spinal cord exhibits subtle cervical and lumbar

(lumbosacral) enlargements produced by extra neurons in segments that innervate limbs. Theregion of spinal cord caudal to the lumbar enlargement is conus medullaris. Caudal to this, a terminal

filament of (nonfunctional) glial tissue extends into the tail.

A spinal cord segment = a portion of spinal cord that

gives rise to a pair (right & left) of spinal nerves. Each spinal

nerve is attached to the spinal cord by means of dorsal and

ventral roots composed of rootlets. Spinal segments, spinalroots, and spinal nerves are all identified numerically by

region, e.g., 6thcervical (C6) spinal segment.

Sacral and caudal spinal roots (surrounding the conus

medullaris and terminal filament and streaming caudally to

reach corresponding intervertebral foramina) collectively

constitute the cauda equina.

Both the spinal cord (CNS) and spinal roots (PNS) are

enveloped by meninges within the vertebral canal. Spinal

nerves (which are formed in intervertebral foramina) are

covered by connective tissue (epineurium, perineurium, &

endoneurium) rather than meninges.

Spinal cord histology (transverse section):Central canal (derived from embryonic neural cavity) is lined by ependymal cells & filled

with cerebrospinal fluid. It communicates with the IV ventricle and ends in a dilated region (terminal ventricle).

Gray matter (derived from embryonic mantle layer) is butterfly-shaped. It has a high

density of neuron cell bodies & gliocytes, a high capillary density, and sparse myelinated fibers.

Gray matter regions include: dorsal horn, ventral horn, and intermediate substance the latter

features a lateral horn (sympathetic preganglionic neurons)in thoracolumbar spinal segments.

terminal filament

conus medullarislumbar enlargementcervical enlargement

BRAIN

Spinal Cord Section

tractAfferent

neuron

recepto

muscle

cell

body

reflexinterneuron

Efferent neuron

white matter

gray matter

spinal ganglion

dorsal

root(rootlets)

spinal

nerve

ventral

root

(rootlets)


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Types of spinal neurons:All neurons in spinal cord gray matter have multipolar cell bodies. Based on axon destina-

tion, they can be divided into three major types, each of which has several subtypes:

1] Efferent neurons(embryologically derived from basal plate) send axons into the ventral root.

Cell bodies of efferent neurons are located in ventral horn (somatic efferents) or in intermediate

substance (visceral efferents).

somatic efferent (SE) neurons:

alpha motor neurons innervate ordinary skeletal muscle fibers (motor units);

gamma motor neuronsinnervate intrafusal muscle fibers (within muscle spindles);

visceral efferent (VE) neurons: preganglionic sympathetic and parasympathetic neurons.

2] Projection neuronssend axons into spinal white matter to travel to the brain (or to a

distant part of the spinal cord). The axons form tracts associated with ascending spinal pathways that

have different functions.

Projection neurons may be categorized according to the types of stimulation that ultimately

excites them: Someprojection neurons respond specifically to thermal or mechanical mild or noxious stimuli;however, many projection neurons respond non-specifically to both mild and noxious stimuli (they function to maintain

alertness). Some projection neuron respond only to somatic stimuli (exteroceptors or proprioceptors); others respond to

both somatic and visceral stimuli. The latter are the basis for the phenomenon of referred pain.

3] Interneurons have axons that remain within spinal gray matter. Interneurons are inter-

posed between spinal input (from peripheral nerves or brain) and spinal output (efferent neurons).

By establishing local circuits, interneurons "hardwire" input to output and thus determine the inher-

ent reflex responses of the spinal cord (spinal reflexes).

Spinal Pathways

Primary Afferent Neuron= the first neuron in a spinal reflex or ascending spinal pathway.

Primary afferent

neurons have their

unipolar cell bodies in

spinal ganglia. Receptors

are found at the periph-

eral terminations of their

axons. Their axons

traverse dorsal roots,

penetrate the spinal cord

(at the dorsolateralsulcus) and bifurcate into

cranial and caudal

branches which extend

over several segments within white matter of the dorsal funiculus.

Collateral branches from the cranial and caudal branches enter the gray matter to synapse on

interneurons and projection neurons (or directly on efferent neurons for the myotatic reflex).

In some cases (discriminative touch), the cranial branches of incoming axons ascend directly

to the brainstem where they synapse on projection neurons of the pathway.

Spinal Nerve

SpinalGanglion

Dorsal Root

Spinal Cord Cranial branch to brain

Collateral branches to spinal gray mate

Primary Afferent Neuron


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Note:Pathway= sequence (chain) of neurons synaptically linked to convey

excitability changes from one site to another.

Ascending Pathways:Chains of neurons carrying information from receptors to the brain (cerebral cortex).

Neuronal sequence:

Primary afferent neurons synapse on projection neurons typically located in spinal

gray matter. The axons of projection neurons join ascending tractsand synapse on neurons in

the brain. Ultimately, the pathway leads to thalamic neurons that project to the cerebral

cortex.

The function of a particular pathway is determined by: 1] which primary afferent neurons

synapse on the particular projection neurons of the pathway, and 2] where the projection

neurons synapse in the brain.

In general, pathways may be categorized into three broad functional types:

1] Conscious discrimination/localization (e.g., pricking pain, warmth, cold, discriminative

touch, kinesthesia) requires a specific ascending spinal pathway to the contralateral thalamus which,

in turn, sends an axonal projection to the cerebral cortex. Generally there are three neurons in the

conscious pathway and the axon of the projection neuron decussates and joins a contralateral tract

(see the first two pathways on the following page; the third pathway is the one exception to the general rule).

2]Affective related (emotional & alerting behavior) information involves ascending spinal

pathways to the brainstem. Projection neurons are non-specific. They receive synaptic input of

different modalities and signal an ongoing magnitude of sensory activity, but they cannot signal

where or what activity.

3] Subconscious sensory feedback for posture/movement control involves ascending spinal

pathways principally to the cerebellum or brainstem nuclei that project to the cerebellum. Generally

there are only two neurons in a subconscious pathway and the axon of the projection neuron joins an

ipsilateral tract (see the last pathway on the following page).

Descending Spinal Pathways:

Axons of brain projection neurons travel in descending tracts in spinal white matter. Theyarise from various locations in the brain and synapse primarily on interneurons.

By synapsing on interneurons, descending tracts regulate:

1] spinal reflexes;

2] excitability of efferent neurons (for posture and movement); and

3] excitability of spinal projection neurons, i.e., the brain is able to regulate sensory

input to itself.In some cases, descending tracts affect axon terminals of primary afferentneurons, blocking release of neurotransmitter (presynaptic inhibition).


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Lecture 5

Spinal Reexes &

Neuronal Integration

Reex an n erent, su consc ous, re at ve y cons stent responses to a part cu ar st mu at on.

Reexes may be categorized as:

somatic nvo v ng s e eta m.) or autonomic mpact ng v scera); an as

rainstem nvo v ng cran a nn.) or pinal nvo v ng sp na nn. an t e sp na cor )

In contrast . . .

Reaction = an inherent, subconscious, relatively consistent responses to a particular stimula-

t on, nvo v ng t e cere e um an cere ra cortex; e.g., opp ng react on & tact e p ac ng react on.

Examp es o ra nstem re exes nc u e:

eye s c ose w en t e cornea s touc e cornea re ex

lip moves in response to a noxious stimulation (pin prick)

Examp es o sp na re exes, nvo v ng sp na nerves an t e sp na cor , nc u e: extensor t rust: paw propr oceptors tr gger extens on

pann cu us re ex: pr c ng s n tr ggers contract on o cutaneus trunc m.

myotat c re ex: musc e stretc s res ste y contract on o t e musc e

w t rawa re ex: m s w t rawn rom a nox ous st mu us

NOTE:

Re ex responses are eterm ne y nterneurons w c ar -w re a erent nput to e erent

output. Interneurons organ ze e erent neurons motor un ts) nto mean ng u movement components,

which can be utilized by either spinal input or descending pathways.

S nce "vo untary movement" an " nvo untary re ex react on" compete or contro o t e

same nterneurons c rcu ts, t ey cannot e n epen ent on one anot er. T us, ra n act v ty w

n uence sp na re ex responses, ma ng re ex eva uat on an nterpret ve art.

Withdrawal Reex = Flexor (Crossed Extensor) Reex

Features o t e re ex agramme on t e next page) nc u e . . .

pr mary a erent neuron 1) part c pates n ot re exes 2) an ascen ng pat ways 3);

vergent nterneurona c rcu t propagates to severa segments an r g t an e t s es;

positive feedback prolongs the reex beyond the time of the stimulus (A); n v ua nterneurons are e t er exc tatory or n tory ac ce s) n t e r e ect;

antagon sts are n te w e agon sts are exc te rec proca nnervat on D);

escen ng pat ways C) mo y re ex c rcu t re ex s not n epen ent o ra n contro ).

NOTE:As the reex is tested clinically, the crossed extensioncomponent disappears after

t e rst 3 wee s o age as escen ng pat ways mature; ut ater n e, t e nor-

ma y n te crosse extens on reappears upstream amage to escen ng

ers removes t e n t on.


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ACKGROUND PROPRIOCEPTIVE INFORMATION

Proprioceptors are mec anoreceptors, ocate n musc es ten ons & o nt capsu es gaments.

ropr oceptors prov e:

su conscious ee ac a out t e status o musc es & o nts,

consc ous inest esia sense o pos t on & movement), an

pain

Joint receptors: ree nerve en ingst at respon to extreme movement or n ammat on (pain

ncapsu ate receptors:

tonic: signal joint position

p as c: respon to rate o c ange n o nt pos t on arge ysu conscious

Muscle & tendon receptors:

ree nerve en ngs : pa n

(Golgi) tendon organs located in series with muscle bers (tension detector)

musc e sp n es: ocate n musc e e y (length detector)

Withdrawal Reex

flexor

extensor

flexor

extensor

DL F.

DL Sulcus

1

2

3

A

B

C

D D


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Myotatic Reex

n ca y, a myotat c re ex s e c te y a rupt y tapp ng a ten on e.g., t e pate ar ten on .

u en y e orm ng sp ac ng a ten on e ect ve y stretc es t e assoc ate musc e.

en a w o e musc e s su en y stretc e as a resu t o ten on e ormat on , annu osp rareceptors n musc e sp n es are s mu taneous y exc te , tr gger ng a vo ey o act on potent a s n

Aa erent axons. t n t e , t e axons act vate exc tatory synapses on a p a motor neurons

t at nnervate t e musc e t at was stretc e . so, a p a motor neurons to antagon st c musc es are

inhibited via interneurons. As a result, the stretched muscle immediately contracts.

us, e myotat c re ex unct ons to oppose musc e stretc . nce nterneurons are

y-passe n e c t ng t e contract on, t e response s rap , oca ze , an re at ve y res stant to y-

pox a, at gue, rugs, etc.

endplat

eending

s

trailen

dings

Myotatic Reflextendon

extrafusal

muscle fiber

GAMMAneurons

ALPHA neurons

II

a

b

same muscle

antagonist muscle

reticulo-spinal tractfrom brain


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Reex sensitivity:

Sens t v ty o t e myotat c re ex t e extent to w c a musc e can e stretc e e ore t re-

exly contracts) is determined ultimately by the contractile state of the polar regions of the intrafusal

muscle bersbecause the degree of contraction of the polar regions determines the pre-existing

as egree o stretc o ntra usa centra reg ons) w en t e w o e musc e s stretc e .

T us, s nce gamma neurons nnervate ntra usa po ar reg ons, sensitivity of the myotatic

reex is set by the frequency of AP's in axons of gamma neurons, an gamma neuron exc ta ty

is controlled by descending tracts from the hindbrain (reticulospinal tracts & vestibulospinal tracts)

Functions of the myotatic reex:

usc e one t e res stance musc es o er w en e ng stretc e engt ene ) the resistance encountered when an appendage is manipulated

tone s set y: ra n > escen ng pat ways > gamma neuron r ng rate

ormal tone is variable, ut appropr ate to t e an ma s current e av ora state

. yperton a spast c ty) = xe excess ve tone, .e., excess res stance to man pu at on

due to excessive gamma neuron excitation (rate of ring)

or ypoton a "wea ness") = xe e c ent tone, e.g., rag- o appen ages

t e resu t o nsu c ent gamma neuron exc tat on.

Posture maintenance un er c anging con itions o oa & atiguey us ng myotat c re exes, t e ra n s a e to set musc e engt s an x o nt pos t on .e.,

posture) w t out concern or oa an at gue. T e ra n sets engt s o ntra usa musc e ers to

correspond to desired whole-muscle lengths.Any musc e t at s onger t an t e es re engt w ave ts sp n e receptors act vate an

t e resu tant myotat c re ex w pers st unt t e musc e as s ortene to t e proper engt . A ter

posture s set, motor neurons w rece ve a urst o exc tatory synapt c nput w enever a musc e

becomes stretched and they will lose that excitation once the muscle shortens sufciently.

y ana ogy, t s s a servosystem, e.g., one sets a t ermostat t e ra n sets gamma neuron

exc tat on to contro a urnace myotat c re ex to ma nta n a es re temperature posture .

Voluntary movement or s ow movements, posture can e sequent a y a uste to pro uce movement, e.g.,

n m scratc ng t e an ; earn ng any new movement sequence; etc. For a rupt vo untary

movements, the brain co-activates alpha & gamma neurons to maintain spindle sensitivity whilemusc es s orten sp n es re ur ng movement). Gamma neurons myotat c re exes) must e n -

te n antagon st c musc es as agon sts are exc te .

Clinical Considerations

A c n c an taps a ten on n or er to :

) ver y t e ntegr ty o oca per p era nerves an sp na cor segments; an

) eva uate ra n contro an t e ntegr ty o escen ng tracts

oo ng part cu ar y or ev ence o xe yperton a or ypoton a.


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Neuronal Integration

A typ ca mu t po ar neuron n t e CNS rece ves many t ousan s o synapt c nputs exc tatory

n tory; axosomat c axo en r t c; rom nterneurons pro ect on neurons; etc. . How oes a neuron ntegrate a

o ts verse synapt c nput? How oes t ma e "sense" o t e vers ty an " re" appropr ate y to

effectively inuence other neurons in its circuit? The answer neuronal integrtion.

Synaptic inputs predominantly on dendrites & soma (receptive zone): axosomat c exc tatory synapses epo ar ze ent re soma ce o y) sur ace. T e

ce o y acts e a sp ere c arges ons str ute even y over a sp er ca sur ace). t oug eac EPSP a ects t e w o e soma, a s ng e EPSP as a very m te e ect.

axo en r t c exc tatory synapses epo ar ze pre erent a y towar t e soma. T e EPSP s

pass ve y con ucte towar a ower res stance asymmetr ca ameter = asymmetr ca res stance .

NOTE:

In tory synapses e ave e exc tatory ones,

except t at t ey pro uce IPSPs t at yperpo ar ze

t e soma an cance EPSPs).

Neuronal output:

an act on potent a (AP)or g nates at t e n t a segment o t e axon w ere g ens ty o

vo tage-gate Na c anne s are present;

t e n t a segment s great y n uence y t e mass ve soma a acent to t, .e., t e soma

continually depolarizes or hyperpolarizes the initial segment at each instant of time;

w enever t e n t a segment reac es t res o epo ar zat on, t generates an APt at

trave s a ong t e ent re axon.

us, the soma membrane of each neuron integrates total syn-

aptic input at each moment of time! ntegration is the result of

algebraic summation of synaptic activity (EPSPs and IPSPs). The

oat ng soma mem rane potent a re ects t e net exc tatory an

n tory synapt c nput to a part cu ar neuron at a part cu ar t me.

T e magn tu e o soma epo ar zat on an ana og signa ea or ntegrat on)

s converte to requency o APs a ong t e axon a igita signa ea or

stance con uct on).

Factors inuencing synaptic effectiveness: or a g ven compet ng nput source, mpact on a target neuron epen s on:

) number of source synapses on the target neuron;

2) locations of source synapses on the target neuron.

or an n v ua synapse, e ect veness s re ate to synapt c ocat on on t e target neuron

most effective {axon hillock >> soma >> proximal dendrite >> distal dendrite} least effective

a g ven amount o synapt c nput w ave more e ect n a sma vs. arge) neuron ce o y;

t us, w t n a neurona poo , sma neurons are recru te rst, arge neurons ast.


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synapt c e ect s ncrease y repet t ve r ng tempora summat on);

synaptic effect is increased by collaborative ring of different sources (spatial summation).

Temporal summation: repeate synapt c nput can sum to pro uce an ncrease e ect, w en

su sequent PSPs arr ve e ore prev ous PSPs comp ete y ecay.

Spatial summation: synapt c nput rom a secon source can sum w t t at o a pr mary source to

pro uce an ncrease e ect.


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III. Motor Efferent Nuclei(Basal Plate Derivatives):

1. SE (Somatic Efferent) Nuclei:SE neurons form two longitudinally oriented but discon-

tinuous columns of cell bodies in the brain stem. The neurons that comprise these columns are

responsible for innervating all of the skeletal musculature of the head.Refer to the diagram on page

46 for the location of brain stem nuclear columns.

A) Oculomotor, Trochlear, Abducent and Hypoglossal Nuclei are formed by a column

of cells located near the dorsal midline of the brainstem. The nuclei innervate muscles of the tongue

and eye which are derived from somites. Damage or lesions to these nuclei or their nerves (III, IV,

VI, and XII) result in the following clinical signs:

1) Oculomotor, trochlear or abducent (cranial nerves III, IV, &VI): Abnormalities

in eye movement, deviation of the eyes (strabismus).

2) Hypoglossal (XII): Paralysis and atrophy of tongue muscles; deviation of

tongue toward the side of damage, problems chewing & swallowing.

Comparison of the four major cell columns in the spinal cord with the more complicated

picture seen in the brainstem. Note that the adult location of the alar derivatives (sensory

nuclei) is located laterally in the brainstem instead of dorsally as it is in the spinal cord.

B) Motor Nucleus of the Trigeminal N.(cranial nerve V), Facial Nucleus(cranial nerve

VII) and Nucleus Ambiguus(cranial nerves IX & X) are formed by a column of cells located in

the ventrolateral brainstem. This location results from the ventrolateral migration of the cell columnduring development. These neurons innervate muscles derived from somitomeres in pharyngeal

arches. (Formerly this cell column was regarded as (SVE)).

Damage or lesions involving these nuclei or their nerves result in the following clinical signs:

1) Motor nucleus of the Trigeminal N.: innervates muscles of mastication and

damage to it or the trigeminal nerve results in paralysis of these muscles

and associated muscle atrophy (bilateral damage results in dropped jaw).

GSAGVA

SE

VE

SE (SVE)

olivary

nucl.

GSAGVA

SEVE

IV

alar

plate

basal

plate

spinal cord brain stem

Afferent and Efferent Nuclei


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2) Facial nucleus: Innervates muscles of facial expression (ears, eyelids, nose

& lips); damage to the nucleus or facial nerve results in facial paralysis.

3) Nucleus Ambiguus: innervates muscles of the soft palate, larynx, and

pharynx (involved with speech, coughing, swallowing & gag

reflexes); damage results in swallowing and vocalization difficulties.

2. VE (Visceral Efferent) Nuclei:Represent the cranial portion of the parasympathetic

division of the autonomic nervous system (preganglionic parasympathetic neurons). Four nuclei are

recognized, but only two are important to remember: the parasympathetic nucleus of the vagus

nerve and the parasympathetic nucleus of the oculomotor nerve.

The parasympathetic nucleus of the vagus innervates cervical, thoracic and abdominal

viscera while the parasympathetic nucleus of III innervates pupillary constrictor muscle and the

ciliary body muscle of the eye:

1) Parasympathetic nucleus of III damage causes loss of pupillary

contriction in response to light in the eye on the side of the lesion.

2) Parasympathetic nucleus of X damage results in accelerated heart rate,

increased blood pressure, and disturbances of gastrointestinal activity.

IV. Sensory Afferent Nuclei (Alar Plate derivatives):

1. GSA (General Somatic Afferent) Nuclei:Represented by the sensory trigeminal com-

plex which is located quite laterally in the brain stem. The complex is composed of the following

three major subdivisions:

a) Nucleus of the spinal trigeminal tract (spinal trigeminal nucleus)located in the

medulla; associated predominately with pain and temperature sensation from the face and oral

cavity; damage to this nucleus results in loss of pain and temperature sensation from half the face.

b) Pontine nucleus of the trigeminal nerve (principal sensory nucleus)located in

the pons; associated with touch and pressure sensation from the face and oral cavity; damage result

in loss of touch and pressure sensation from the face.

c) Mesencephalic nucleus of the trigeminal nerve: located in the midbrain, receives

proprioceptive information from the face.


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2. GVA(General Visceral Afferent) Nucleus:Located lateral to the GVE column and

comprised of a single nucleus termed the nucleus of the solitary tract (nucleus solitarius). The GVA

portion of this nucleus is associated with cranial nerves IX and X. It mediates visceral sensation from

the pharnyx, larynx and portions of the esophagus.

3. SVA (Special Visceral Afferent) Nuclei:

A. There is a taste SVA component in the nucleus of the solitary tract. Taste is associ-

ated with cranial nerves VII, IX and X which convey taste from the tongue and pharynx. Lesions or

damage to the nucleus solitarius will disrupt taste sensation.

B. The olfactory nerve is associated with olfactory SVA sensation. This nerve how-

ever is not foundf in the brainstem; rather, olfaction is conducted directly to the piriform lobe of the

telencephalon. Lesions or damage to the olfactory nerve will interrupt olfaction.

4. SSA (Special Somatic Afferent) Nuclei: These brain stem nuclei relate to the sense of

vision (lateral geniculate nucleus), the sense of hearing (cochlear nuclei) and the ability to maintain

balance (vestibular nuclei).

The medullary SSA column related to hearing and balance is located dorsally and laterally in

the brain stem and is related to cranial nerve VIII.

The SSA nucleus related to vision is located in the thalamus and is associated with the optic

nerve/tract input. Obviously damage to cranial nerves II or VIII or their associated nuclei will have

profound effects on the animals ability to see or hear, respectively.

Diagram indicating the nuclear columns in

the brain stem and illustrating the type of

structures supplied by the different catego-

ries and the nerves containing fibers from

the different nuclear columns.

somatic

efferent

skin

(GSA)

taste

(SVA)

(GVA)

inner ear

(SSA)

visceral

efferent

somati

c

eff

vis

ceral

eff

visc

era

laff

som

atic

aff

.

Cranial Nerve

Cell Columns


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tectum

p.IX

p.X

III

IV

VI

XII

motorV

VII

n.amb.

XI

n.sol.tr.

n.sp.tr.V

n.pon.sen.V

thalamus

optic

chiasma

p.VII

p.III

mes.tr.V

inte

rn

al

capsul

e

n.mes.tr.V

sp.tr.V

genu VII

III

ventricle

pon

s

V

VII

olivary nucl.

VI

facial nerve

olivary nucl.

genu VII

pons

vestibular

nucl.

rostral

colliculus

crus cerebri

dorsal nucl.trapezoid body

Sensory (left) and Motor (right) Cranial Nerve Nuclei


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Lecture 7

Vestibular System

Introduction:The vestibular system is responsible for maintaining normal position of the eyes and head as

external forces tend to displace the head from its normal position. Located within the inner ear, the

vestibular apparatus is the sense organ that detects linear and angular accelerations of the head and

relays this information to brainstem nuclei that elicit appropriate postural and ocular responses.Note: Because [force = mass acceleration] and because head mass is constant, detecting head

acceleration is equivalent to detecting external force to the head.

Inner Ear Anatomy:The inner ear is called the labyrinth because it consists of channels and chambers hollowed

out within the temporal bone. The labyrinth has osseous and membranous components:

Osseous Labyrinth tubes and chambers in the petrous part of the temporal bone that

contain perilymph fluid and house the membranous labyrinth. The three osseous components are:

1) Cochlea a spiral chamber that is related to hearing and will be discussed later

2) Vestibule a large chamber adjacent to the middle ear

3) Semicircular Canals three semicircular channels in bone, each semicircular

canal is orthogonal to the other two

Schematic diagram of the osseous labyrinth containing the membranous labyrinth. The

vestibule relationship (left) and the semicircular canal relationship (right) are shown.

Membranous Labyrinth consists of interconnected tubes and sacs that are filled with

endolymph, a fluid high in potassium. (Fluid outside the membranous labyrinth is perilymph, which

is low in potassium and high in sodium like typical extracellular fluids.)

boneperilymph fluid

memb. labyrinthendolymph fluid

otolith memb.macula

cupulamembrane

cristaampularis semicircular

duct

UTRICLE

BONE


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The membranous labyrinth, which contains

the sense organ receptor cells, consists of the follow-

ing components:

1) Cochlear Duct related to hearing (will

be discussed later).

2) Utricle larger of two sacs located in the

vestibule

3) Saccule smaller of two sacs located in

the vestibule

4) 3 Semicircular Ducts each duct is

located within one of the semicircular canals. Each

duct has a terminal enlargement called an ampulla

which contains a crista ampullaris, a small crest

bearing sensory receptor cells.

Vestibular Apparatus:

Vestibular apparatus is a collective term for sensory areas within the membranous labrinth

responsible for detecting linear acceleration (e.g., gravity) and angular acceleration of the head.

The vestibular apparatus consists of:

1) macula of the utricle the sensory area (spot) located in the wall of the utricle; it is

horizontally oriented and detects linear acceleration in the horizontal plane (side to side).

2) macula of the saccule the sensory spot in the wall of the saccule; it detects linear

accelerationin the vertical plane (up and down).

3) crista ampullaris one per semicircular duct ampulla; each detectsangular acceleration

directed along the plane of the duct.

Schematic illustraion of a macula, including neurons of the vestibular nerve. Two types

of receptor (hair) cells have stereocilia that extend into the overlying otolith membrane.

kinocilium

efferent

otolith membrane

vestibularnerve

vestibular

ganglion

bipolar

CNS

Ducts


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CNS Connections:Vestibular nerve fibers (axons from neuron cell bodies of the vestibular ganglion) travel from

the inner ear to the brain. They synapse in vestibular nuclei of the brainstem and in the nodulus

or flocculus of the cerebellum.

Vestibular nuclei:

Four vestibular nuclei are located bilaterally in the medulla oblongata and pons. They receiveinput from the vestibular nerve and project to:

1) cerebellum,

2) reticular formation,

3) spinal cord via the lateral vestibulospinal tract (which activates limb extensor

muscles via alpha and gamma neurons), and

4) neurons controlling eye (3, 4, and 6 cranial nerves) and neck (cervical spinal cord)

muscles via the medial longitudinal fasciculus.

rostral lateral caudal

(descending)

medial

Four Vestibular Nuclei

(lateral view)

medial

rostral

lateral

caudal

oculomotor

trochlear

abducent

thalamus

cerebellarpeduncles

lateral vestibulospinaltract

reticulospinal tracts

medial longitudinal fasiculus(mlf)

Spinal Cord

III

IV

VI


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Lecture 8

Posture & Movement

In veterinary neurology, abnormalities of posture & movement are more important than sensory

disorders because animals readilty express motor behavior but hardly at all report their feelings.

Preview: Posture/Movement Hierarchy

Spinal Cord and Cranial Nerve Motor Nuclei

Local reflexuseful response to a stimulus (determined by local interneuronal circuits).

Hindbrain

Standing postureexcitation of alpha & gamma motor units of extensor muscles

(driven by spontaneous activity of reticular formation & vestibular neurons).Equilibriummaintaining normal position of eyes, head, & body (vestibular system).

Midbrain

Orientationorienting head/eyes/ears toward abrupt visual/auditory stimuli (tectum).

Specific movementsmoving individual joints (via red nucleus and rubrospinal tract).

Forebrain

Inherent movement sequencesspecies-specific patterns of posture/movement/gait

(basal nuclei interacting with thalamus & motor areas of cerebral cortex).

Learned movementsincluding learned movement sequences performed too rapidly

for sensory feedback (involves premotor cerebral cortex).

Brain Structures Concerned with Posture & Movement

----------------------------------------------------------------------------------------------------------- Hindbrain

Reticular FormationAnatomy:network (mixture) of gray & white matter, found throughout the brainstem synaptic input from collateral branches of ascending tracts (e.g., spinothalamic tract)

Physiology:spontaneously active neuronal circuits; perform three major functions:

ascending system to alert cerebral cortex (via non-specific thalamic nuclei) vs. coma

vegetative centers: regulate heart rate, respiration, digestion, micturition, etc.

standing posture and muscle tone via pathways to alpha & gamma neurons:

two divisions the lateral one is spontaneously active & dominant:

1} located laterally in pons & medulla: pontine reticulospinal tract

activates alpha & gamma motor units of extensor muscles

2} located medially in medulla: medullary reticulospinal tract inhibits neurons to extensor mm. & excites neurons to flexor mm.;

not spontaneously active driven by cerebral cortex

Vestibular nuclei discussed previouslyTwo descending tracts: lateral vestibulospinal tract which also drives standing posture, &

medial vestibulospinal tract (m.l.f.) which controls neck muscles.Vestibular nuclei also utilize the two reticulospinal tracts to adjust muscle tone.


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-------------------------------------------------------------------------------------------------------------Midbrain

Red nucleusThe nucleus gives rise to the rubrospinal tractthe principal descending tract for voluntary

movement in domestic animals. (Rubrobulbar fibers go to cranial nerve motor nuclei.)

The red nucleus is merely a collection of projection neurons. Axons from the motor area of

cerebral cortex synapse on neurons of the red nucleus and control their activity.

The rubrospinal tract decussates in the midbrain and descends in the dorsal half of the lateralfuniculus. Rubrospinal fibers synapse on spinal interneurons and produce independent movements of

shoulder/hip; elbow/stifle; and carpus/hock (not digits).

Tectum (tectum = roof of the midbrain)Rostral & caudal colliculi give rise to two tracts (which arise from rostral colliculus):

1} tectospinal fibersdescend to the cervical spinal cord (head turning);

2} tectobulbar fibersto cranial nerve nuclei that control ear & eye movement.

Substantia nigra

Functions like a basal nucleus (see below).It has reciprocal connections with the striate body (caudate &

putamen), where its telodendria release the neurotransmitter dopamine. Deficiency of dopamine in primates

results in Parkinson's Disease (hypokinesia, rigidity, tremor).

------------------------------------------------------------------------------------------------------------Forebrain

SubthalamusFunctions like a basal nucleus (see below). It play a role in producing rhythmic movements such as are employed in

locomotion. In primates, lesions (damage) to subthalamus result in involuntary release of large flailing movements

(hemiballismus).

Basal nucleiThree basal nuclei (caudate, putamen, & pallidum or globus pallidus) are associated with move-

ment. The nuclei do not give rise to descending tracts. Instead they participate in forebrain circuits inwhich they communicate with cerebral cortex via thalamic nuclei.

Damage to basal nuclei impairs coordinated movement by affecting the magnitude, timing and

sequencing of individual components of a movement. (In domestic animals, lesions of the basal

nuclei usually result in circling to the affected side.)

StriatBody

LentiformNucleus

Caudate

Putamen

Globus Pallidus

Amygdaloid

Claustrum

Anatomically, the term "Basal Nuclei"

refers to non-cortical gray matter of the

telencephalon. There are five major nuclei (and

several smaller ones).

The major nuclei can be anatomically

subgrouped in different ways:1] Striate body (gray matter connecting

caudate & putamen produce striations in the

intervening internal capsule).

2] Lentiform nucleus (the putamen and

globus pallidus together have the shape (form)

of a lens.

Physiologically, only caudate, putamen,

and globus pallidus play a motor role.


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Functionally, basal nuclei are involved in two separate circuits:

one, involving the caudate nucleus, is active in selecting & assembling movements;

the other,involving putamen, regulates amplitudes & durations of movement components.

Note: Caudate nucleus & putamen both inhibit globus pallidus which, in turn, inhibits

thalamic neurons that project to motor related areas of cerebral cortex.

Cerebral cortexMotor-related areas of cerebral cortex:

motor arealocated around the cruciate sulcus; principal source of output for all voluntary

movement; it's the main source of two descending pathway systems (below)premotor arealocated in frontal lobe rostral to the motor area; required for re-calling

learned, rapid-sequence movements (particularly involving distal muscles).

supplementary motor arealocated medial to premotor area; active when thinking

about a proposed movement; projects to motor area

Descending pathways for voluntary movement fall into two categories:

1] Pyramidal tract = a direct connection from primary and other motor areas of cerebral cortex to

efferent neurons, generally via local interneurons. Axons travel in the pyramid of the medulla oblon-

gata. Most axons decussate at the medullary-spinal junction (lateral corticospinal tract); some cross

at the level of termination in the cord (ventral corticospinal tract). The tract controls particularly

musculature of the manus and pes. It is concerned with fine (vs. coarse), precise movements.Some corticospinal axons affect projection neurons of

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