Cell body

EndoplasmicreticulumNucleus

Lysosome

Golgicomplex

Microtubular “highway”

Axon Debris

Secretoryvesicle

Axonterminal

Axoplasmic transport

Neurocytology & Tract-tracing

Widely used techniques for studying neurons and circuits:

Visualization of neurons Nissl staining, Golgi methods,

intracellular dye injections, immunohistochemistry

Degeneration and reactive changes in the neuron after lesion

Wallerian degeneration

Axonal transport methods

Autoradiography, HRP, Lectins, Biocytin, Dextrans, Fluorescent Tracers

Neuronal cell bodies: Nissl method

The Golgi method

cerebellarPurkinje cell

Intracellular injectionof Lucifer Yellow

Biolistics (“gene-gun”)

Immunohistochemistry

PEP-19 antiserum reveals the calyx of Held

L7 protein reveals cerebellar Purkinje cells

Tract-Tracing

Anterograde Degeneration:Reduced silver

method and

electron microscopy

Anterograde Walleriandegeneration

Retrogradedegeneration

AnterogradeTract-tracing Autoradiography

Anterogradetransport

Uptake by Cell body

Collateralprojections

Labeledterminals

Radioactively labeled amino acid

RetrogradeTract-Tracing HRP, Dextran

Retrogradetransport

HRP

Uptake by terminals

Tract-tracing:

Fluorescent tracers

Combining techniques at the LM and EM level

Protection of the CNS

• The cranium encloses the brain, and the vertebral column encloses the spinal cord.

• The CNS is wrapped by several meninges: the outer dura mater, the middle arachnoid mater, and the innermost pia mater.

• The brain is surrounded by (and suspended in) the cerebrospinal fluid (CSF).

• The blood-brain barrier limits access of blood-borne substances to the brain.

Cranial cavity: contents• The cranial cavity (and vertebral canal) are closed,

relatively isolated spaces.• Basic boundary is the arachnoid mater• Contents include:

Brain and spinal cord (intra- and extracellular fluid) CSF Blood

dura

arachnoid

CSF formation = ~500 ml/day

brain = 1500 ml (1200 ICF; 300 ECF)

CSF = 125 ml (30 in ventricles)

blood = 80 ml

Right lateralventricle

Left lateralventricle

Central canalof spinal cord

Fourth ventricle

Third ventricle

The CSF is formed and circulates in the

ventricles.

• It is produced by the choroid plexuses inside the ventricles, and circulates through the ventricles.

• From the fourth ventricle it enters the subarachnoid space, between the arachnoid mater and pia mater.

• Arachnoid villi in this space drain the CSF into the blood.

Subarachnoid space of brain

Arachnoid villus

Dural sinus

Pia mater

Dura mater

Arachnoid mater

Scalp

Skull bone

Venous sinus

Brain (cerebrum)

CSF composition• clear and colorless

• little/no protein

• acellular (0-5 wbc/ml is normal)

• low Glucose (30% below plasma)

• Ions: = Na+, Cl, K+, Ca++

(comp. to plasma)

• pH =7.33

• *cloudy, colored, cellular CSF implies pathology

• >80% from choroid plexus

(specialized ependymal cells)

• rate = .3-.4 ml/min

(~500ml total vol./day)

•pressure=<200 mm H2O

CSF production

CSF pathology

•too much anywhere = hydrocephalus

•excess production = quite rare

•impeded circulation = “non-communicating” hc (blockages)

•impeded drainage = “communicating” hc due to failed reabsorption

•leaking from head = skull fracture

•altered composition = bleeds, infections, tumors

Cerebral circulation

• Brain = 3 - 4% of body weight gets 15-18% of cardiac output uses 20% of total O2 consumed

• specialized barrier functions (BBB)

• specific areas which lack BBB

Space containing cerebrospinal fluid

Ependymal cell

Neurons

Oligodendrocyte

Capillary

Microglial cell

Astrocyte

Functional blood-brain barrier

• allows: small lipophilic molecules; substances with mediated transport (amino acids, glucose)

• blocks: large, charged, hydrophilic molecules; some therapeutics (antibiotics)

• imaging can detect “leaks” indicating pathology

Top

Frontofbrain

Corpus callosum

Cerebral cortex

Thalamus(wall of thirdventricular cavity)

Pineal gland

Cerebellum

Hypothalamus

Pituitary gland

Brain stem

Spinal cord

The CNS consists of the brain and spinal cord.

• The outline for brain anatomy is: Brain stem Cerebellum Forebrain

• Diencephalon Hypothalamus Thalamus

• Cerebrum Basal nuclei Cerebral cortex

Table 5.3 (1)Page 144

Hypothalamus

Brain stem

Cerebral cortex

Thalamus(medial)

Basal nuclei(lateral to thalamus)

Cerebellum

Spinal cord

Midbrain

Pons

Medulla

Brain component

Cerebral cortex

Basal nuclei

Thalamus

Hypothalamus

Cerebellum

Brain stem(midbrain, pons,and medulla)

Major Functions

1. Sensory perception2. Voluntary control of movement3. Language4. Personality traits5. Sophisticated mental events, such as thinking memory, decision making, creativity, and self-consciousness

1. Inhibition of muscle tone2. Coordination of slow, sustained movements3. Suppression of useless patterns of movements

1. Relay station for all synaptic input2. Crude awareness of sensation3. Some degree of consciousness4. Role in motor control

1. Regulation of many homeostatic functions, such as temperature control, thirst, urine output, and food intake2. Important link between nervous and endocrine systems3. Extensive involvement with emotion and basic behavioral patterns

1. Maintenance of balance2. Enhancement of muscle tone3. Coordination and planning of skilled voluntary muscle activity

1. Origin of majority of peripheral cranial nerves2. Cardiovascular, respiratory, and digestive control centers3. Regulation of muscle reflexes involved with equilibrium and posture4. Reception and integration of all synaptic input from spinal cord; arousal and activation of cerebral cortex5. Role in sleep-wake cycle

The basal nuclei have an inhibitory role in motor control:

• inhibiting muscle tone throughout the body

• selecting and maintaining purposeful muscle activity while inhibiting useless movement

• monitoring and controlling slow, sustained contractions

• Implicated in Parkinson’s Disease (dopamine deficiency) Increased muscle tone; resting tremors; slow initiation of movement

Frontal lobe

Cingulate gyrus

Fornix

Thalamus

Hippocampus

Temporal lobe

Amygdala

Hypothalamus

Olfactory bulb

The limbic system

• functions with the higher cortex.• plays a key role in emotion.• works with the higher cerebral

cortex to control behavioral patterns.

• the limbic system has reward and punishment centers.

• neurotransmitters in the pathways for emotional behavior include norepinephrine, dopamine, and serotonin.

Median sagittal section of cerebellumand brain stem

Vestibulocerebellum

Spinocerebellum

Cerebrocerebelum

Regulation of muscle tone,coordination of skilled voluntary movement

Planning and initiation of voluntary activity

Maintenance of balance, control of eye movements

Motor cortex

SpinocerebellumInformed ofmotor command

Makes adjustmentsas necessary

Motor commandto muscles

Informed ofactual performance

Activates receptorsin muscles and joints Movement Skeletal muscles

The cerebral cortex has four lobes, each is specialized for different activities.

• The lobes and some of their functions: Occipital lobe- initial processing of visual input Temporal lobe - integration of multiple sensory inputs, primary

auditory cortex, Wernicke’s area Parietal lobe - somatosensory processing. Each region of parietal

cortex receives somesthetic and proprioceptive input from a specific body area, mostly from the opposite side of the body.

Frontal lobe - voluntary motor activity, speaking ability (Broca’s area), and elaboration of thought. Stimulation of different areas of its primary motor cortex moves different body regions.

Frontallobe

Central sulcus

Parietallobe

Parietooccipitalnotch

Occipitallobe

Cerebellum

Brain stem

Temporallobe

Lateralfissure

Occipital lobe

Primary visual cortex

Wernicke’s area

Temporal lobe

Primary auditory cortex

Centralsulcus

Somatosensory cortex

Posterior parietal cortex

Wernicke’s area

Parietal lobe

Figure 5.11 (2)Page 149

Lefthemisphere

Cross-sectional view

Temporal lobe

Sensory homunculus

Primary motor cortex

Centralsulcus

Broca’s area

Frontal lobe

Lefthemisphere

Cross-sectional view

Temporal lobe

Motor homunculus

Other cortices and motor function• supplementary motor cortex - medial surface of hemisphere

anterior to primary motor cortex. Preparatory role in programming complex sequences of movements.

Stimulation results in complex movement patterns. Lesions do not result in paralysis, but interfere with integration.

• premotor cortex - lateral surface of hemisphere anterior to primary motor cortex. Orienting body and arms toward specific targets. Must be informed of body’s

current position in relation to target. This information is relayed by the posterior parietal cortex.

• posterior parietal cortex - posterior to the primary somatosensory cortex. Integration of somatosensory and visual input- important for complex

movements.

Supplementary motor area Primary motor cortex

Centralsulcus Posterior parietal cortex

Frontal lobe

Premotor cortex

Association areas of the cortex carry out many higher functions:

• prefrontal association cortex - functions include planning for voluntary activity, decision-making, creativity, and developing personality traits.

• parietal-temporal-occipital association cortex - integrates somatic, auditory, and visual sensations from these three lobes.

• limbic association cortex - involved with motivation, emotion, and memory

Centralsulcus

Parietal-temporal-occipitalassociation cortex

Limbic association cortex

Prefrontal association cortex

Sensory input

Primary sensory areas(somatosensory, 1o visual, 1o auditory cortices)

Higher sensory areas

Association areas

Higher motor areas

Primary motor areas

Motor output

Hemispheric specialization

• The left cerebral hemisphere excels in performing logical, analytical, sequential, and language/verbal tasks

• The right cerebral hemisphere excels in spatial perception and artistic and musical talents.

Different aspects of language are controlled by different cortical areas.

• Broca’s area is responsible for speaking ability.

• Wernicke’s area functions for language comprehension.

• Various language disorders are localized in different regions of the cerebral cortex. Damage to these areas can explain the origin of these disorders.

Facial area ofmotor cortex

Broca’sarea

Bundle ofinterconnecting fibers

Wernicke’sarea

Visual cortex

Angular gyrus ofparietal-temporal-occipitalassociation cortex