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Bio 182- Ecology Unit Outline 1/15/15 1 Nervous System Introduction Introduction 1. Neurology-study of the normal functioning and disorders of the nervous system (NS) 2. Functions: Sesnory, integration, motor, & homeostasis 3. Sensory-detects stimuli such as: touch, pain, heat, light, sound, chemicals, etc a. Any change in an organism’s internal or external environment is called a stimulus 1) Threshold stimulus-a stimulus strong enough to initiate an AP 2) Subthreshold stimulus-a stimulus, but not strong enough to initiate an AP b. Structures that detect stimuli are receptors c. Neurons that conduct information from receptors towards the Central Nervous System (CNS) are classified as sensory neurons 4. Integration-processing of all incoming sensory information and initiating an action a. Duty of CNS: brain & spinal cord b. Interneurons (= association neurons) allows communication between sensory and motor neurons 5. Motor-initiates a response to stimulus using effectors: muscles or glands a. Neurons that conduct information away from the CNS towards effectors are classified as motor neurons 6. Sensory and motor neurons comprise the Peripheral NS (PNS) 7. Organization a. CNS 1) Brain 2) Spinal cord 3) Uses interneurons b. PNS 1) Afferent (sensory) system-carries AP’s from receptors to the CNS; uses sensory neurons a) Visceral afferent-sensory information is transmitted from internal receptors to the CNS b) Somatic afferent-sensory information is transmitted from peripheral receptors (in skin & muscles) to CNS 2) Efferent (Motor) system-carries AP’s from the CNS out to effectors; uses motor neurons a) Somatic motor (efferent)-motor information is transmitted from CNS to skeletal muscle b) Autonomic-motor information is transmitted from CNS to cardiac and smooth muscles and glands i. Parasympathetic (PS)-rest & digest

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Bio 182- Ecology Unit Outline 1/15/15 1

Nervous System IntroductionIntroduction 1. Neurology-study of the normal functioning and disorders of the nervous system (NS) 2. Functions: Sesnory, integration, motor, & homeostasis 3. Sensory-detects stimuli such as: touch, pain, heat, light, sound, chemicals, etc

a. Any change in an organism’s internal or external environment is called a stimulus 1) Threshold stimulus-a stimulus strong enough to initiate an AP

2) Subthreshold stimulus-a stimulus, but not strong enough to initiate an AP

b. Structures that detect stimuli are receptors c. Neurons that conduct information from receptors towards the Central Nervous System (CNS) are classified as sensory neurons

4. Integration-processing of all incoming sensory information and initiating an action a. Duty of CNS: brain & spinal cord

b. Interneurons (= association neurons) allows communication between sensory and motor neurons

5. Motor-initiates a response to stimulus using effectors: muscles or glands a. Neurons that conduct information away from the CNS towards effectors are classified as motor neurons

6. Sensory and motor neurons comprise the Peripheral NS (PNS) 7. Organization a. CNS 1) Brain 2) Spinal cord 3) Uses interneurons b. PNS

1) Afferent (sensory) system-carries AP’s from receptors to the CNS; uses sensory neurons

a) Visceral afferent-sensory information is transmitted from internal receptors to the CNS b) Somatic afferent-sensory information is transmitted from peripheral receptors (in skin & muscles) to CNS

2) Efferent (Motor) system-carries AP’s from the CNS out to effectors; uses motor neurons

a) Somatic motor (efferent)-motor information is transmitted from CNS to skeletal muscle b) Autonomic-motor information is transmitted from CNS to cardiac and smooth muscles and glands i. Parasympathetic (PS)-rest & digest

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ii. Sympathetic (S)-fight or flight Nerve CellsNerve Cells 1. Two kinds: a. Neurons that conduct AP’s

b. Neuroglia cells that support, protect, nourish, and enhance the function of neurons 1) Schwann cells a) Location: PNS axons b) Plasma membrane wraps many times around an axon

c) Collection of all Schwann cells that cover an axon is called the myelin sheath

i. Axons that have a myelin sheath are said to be myelinated ii. Spaces between Schwann cells are called Nodes of Ranvier

d) Functions: i. Increase velocity of AP’s (> 100 m/sec ii. Phagocytic during axon repair 2) Oligodendrocytes a) Location: CNS axons b) Forms myelin sheath of CNS neurons c) Each wraps processes around many nerve fibers (axons) d) Functions: i. Increase speed of AP’s (> 20m/sec) ii. Supports 3) Myelin Sheath a) Insulating layer around a nerve fiber b) Oligodendrocytes in CNS & Schwann cells in PNS

c) Formed from wrappings of plasma membrane (20% protein & 80% lipid so it has white color) d) In PNS, 100’s of layers wrap an axon e) In CNS, no neurilemma or endoneurium are present f) Gaps between myelin segments = Nodes of Ranvier g) All axons are in contact with Schwann cells or Oligodendrocytes, but some are not wrapped as much-ones not wrapped as much are said to be unmyelinated h) Myelinated axons, because of high lipid content, appear white; this tissue is collectively called white matter i) Unmyelinated axons have much less lipid content and are more gray in color; this tissue is called gray matter j) Myelination begins during fetal development, but proceeds most rapidly in infancy

4) Astrocytes

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a) Location: CNS b) Two kinds:

i. Protoplasmic astrocytes contribute to blood-brain barrier & regulate composition of tissue fluid ii. Fibrous astrocytes form framework of CNS; these will form scar tissue when neurons are damaged

5) Ependymal cells a) Location: internal cavities of spinal cord & brain b) Resemble a ciliated cuboidal epithelium c) Functions:form and circulate cerebrospinal fluid (CFS) 6) Microglial a) Macrophages formed from monocytes in CNS b) Concentrate in areas of infection, trauma, or stroke 7) Satellite cells a) Uncertain function b) Surround neuron cell bodies of PNS 2. Pathologies a. Multiple sclerosis 1) Degenerative disorder of myelin sheath 2) Oligodendrocytes are replaced by scar tissue

3) Effects vary and part of CNS mostly affected: double-vision, speech defects, tremors, numbness 4) Patients usually die between 7 & 32 yrs 5) Cause unknown, but likely autoimmune

b. Tay-Sachs disease 1) Hereditary disorder mainly in E European Jewish population

2) Abnormal accumulation of glycolipid (ganglioside) in the myelin sheath 3) Normal adults have EZ for breaking down ganglioside, but waste build up leads to signal conduction disruption leading to blindness, loss of coordination, dementia, and death

c. Gliomas 1) Cancerous glial cells are cause of most adult NS tumors

2) Highly malignant and difficult to treat with chemotherapy because of blood-brain barrier (BBB) 3) Radiation or surgery must be used

The NeuronThe Neuron 1. Two main divisions: a. Cell body b. Cell processes-extensions from cell body 1) Dendrites 2) Axon 2. Structure

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a. Cell body (soma)-enlarged area housing nucleus with large nucleolus 1) Full complement of organelles 2) Cytoskeleton of neurofibrils & microtubules 3) ER compartmentalized into NIssl bodies

4) Lipofuscin is product of breakdown of worn-out organelles; accumulates with age 5) A group of cell bodies located outside the CNS is called a ganglion 6) A group of cell bodies inside the CNS is called a nucleus

b. Dendrites-receiving end, highly branched 1) Often associated with receptors 2) Primary site for receiving signals from receptors or other neurons c. Axon-elongate branch, usually single, that extends from cell body 1) Part of neuron that conducts AP’s away from cell body 2) Also called a nerve fiber 3) Group of nerve fibers (axons) outside CNS is a nerve 4) Group of nerve fibers (axons) inside the CNS is a tract 5) Parts:

a) Axon hillock-conical region where axon originates from cell body; has a high concentration of voltage sensitive Na+ channels b) Axon collateral-major, 90 degree, branch of an axon as it nears target organ c) Axon terminal-small, numerous branches near very end of axon (also called telodendria) d) Synaptic end bulb (= synaptic knob, terminal button, synaptic terminals, or synaptic boutons) i. Expanded ends of terminals housing synaptic vesicles

ii. Synaptic vesicles house neurotransmitter (NT) molecules iii. Plasma membrane of an axon is the axolemma iv. Cytoplasm of an axon is the axoplasm v. There are dozens of NT’s known

6) Axonal transport a) Many proteins made in soma (= cell body) must be transported to axon, axon terminals, and SEB; also repair axolemma, for gated ion channels, and as EZ’s or NT’s

b) Fast anterograde axonal transport i. Either direction up to 400 mm/day for organelles, EZ’s, vesicles, and small molecules

c) Fast retrograde for recycled materials & pathogens d) Slow axonal transport or axoplasmic flow

i. Moves cytoskeletal & new axoplasm at 10 mm/day during repair & regeneration in damaged axons

3. Classification of Neurons:

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a. # of processes 1) Multipolar neuron a) Most common b) Many dendrites/one axon 2) Bipolar neuron a) One dendrite/one axon b) Olfactory, retina, & ear 3) Unipolar neuron a) Sensory from skin & organs to spinal cord b) Long myelinated fiber bypassing soma b. Direction of travel 1) Sensory neurons conduct information from receptors to CNS 2) Motor neurons conduct information from the CNS to effectors

3) Interneurons (= association)-confined to CNS; communication between sensory & motor neurons and within CNS

4. Neuron coverings a. Epineurium-CT sheath that surrounds entire nerve b. Perineurium-CT sheath that surrounds a fascicle (bundle of nerve fibers) c. Endoneurium-CT sheath that surrounds each nerve fiber (axon) Neuron PhysiologyNeuron Physiology 1. Resting potential (RP)

a. Neurons and muscle cells are excitable; that is they can send electrochemical messages b. Probes connected to voltmeter measure an internal negative charge (~ -70mV) and an external positive charge (~ +30 mV) along plasma membrane (axolemma) c. This difference in voltage across the plasma membrane is called the resting potential d. How does a neuron (or muscle cell) generate a RP? 1) Other probes that measure ion conc. find:

a) Na+ are more conc. on the outside of the membrane and K+ are more conc. on the inside b) This conc. gradient is caused by the Na+/K+ pump; this pumps uses ATP to transport 3 Na+’s out of the cell and 2 K+’s into the cell

2) RP redefined: difference in charge and ion concentrations between the outside and inside of a neuron not sending a message (AP) 3) What causes negative internal charge? a) The Na/K pump creates a conc. gradient

b) Anions (negatively charged) such as proteins, amino acids, etc are found inside the neuron; these contribute, but are not full explanation

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c) Gated channels (GC) i. Transmembrane proteins across the membrane ii. Na+ GC’s, if open, allow Na+ IN iii. K+ GC’s, if open, allow K+ OUT iv. During RP, GC’s exist in different states v. GC’s have different states of permeability vi. K+ GC are leaky vii. Na+ GC are closed

viii. This difference in leakiness allows + charged K to move out faster than + charged Na moves in ix. Therefore, net interior charge is NEGATIVE x. The membrane is said to be polarized; a form of a cellular battery

2. Action Potential (AP) a. The AP starts at the axon hillock, an area very rich in voltage-sensitive GC’s 1) What kind of stimulus does a voltage-sensitive GC respond to? a) To a change in charge at membrane 2) The GC’s that line the axolemma are voltage-sensitive b. AP’s occur in 2 phases: depolarization and repolarization c. Depolarization

1) Threshold stimulus reaches axon hillock causing voltage sensitive Na+ GC’s to open 2) Na+ rushes IN 3) Na+ ions coming in reverse (from – to +) membrane polarity and are attracted to the next adjacent – area; this movement of Na+ is called ionic flow 4) Na+ entering vicinity of next channel cause voltage shift that opens next voltage-sensitive Na+ GC 5) Na+ enters through GC and ionic flow occurs to next adjacent – region; opens next voltage-sensitive Na+ GC 6) Repeats down entire length of axon as a wave of depolarization 7) Na/K pump is turned off 8) A change from the RP status by depolarization gives rise to the action potential

d. Repolarization 1) As internal voltage approaches +30 mV, Na+ GC close and voltage-sensitive K+ GC’s open allowing + charged K+ OUT 2) This (exit of K+) makes the ECF more + 3) K+ GC’s stay open longer (they are slow GC’s) than Na+ GC’s resulting in a slight overshoot; this overshoot where the internal charge becomes more – than -70mV is called hyperpolarization 4) Na/K pump turns back on and restores ionic imbalances, but is only necessary in the long term

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a) The total movement of ions on any single AP is very small; it takes 100’s of AP’s to change the overall polarity of the membrane

e. AP’s in dominos 1) Analogy: line of dominos-hit first domino hard enough to knock it over, what happens? First domino falls and knocks 2nd domino down which knocks 3rd domino, etc 2) How far does the falling of dominos progress? All the way to the last domino 3) How far do depolarization events progress? All the way to the last voltage sensitive Na+ GC on the SEB 4) Where does the AP start: At the axon hillock, a conical region connected to cell body 5) How would you simulate repolarization with dominos? Have someone set the dominos back up right after they fall 6) How would you simulate a threshold stimulus with dominos? By striking the 1st domino with enough force to knock it over 7) How would you simulate a threshold stimulus with Na+ GC? By having a stimulus of ~ 15 mV that is strong enough to cause voltage-sensitive Na+ GC to open 8) How would you simulate a subthreshold stimulus with dominos? By striking 1st domino with enough force to make it wobble, but not fall over 9) How would simulate a subthreshold stimulus with Na+ GC’s? By having a voltage shift between 1 and 14 mV 10) What are Na+ GC’s doing when activated by lower voltages? They leak, but don’t allow enough + charges in to sustain ionic flow

f. All-or-none principle-a threshold stimulus causes the AP to proceed all the way from the axon hollick to the SEB and a subthreshold stimulus does not send the AP at all g. AP Graph 1) Probe that measures voltage is beneath (inside) plasma membrane 2) A-RP

3) B-Na+ gated channels begin to leak as stimulus occurs; once enough positive charges have entered the area to raise the voltage from -70 to -55 mV 4) C-depolarization is initiated; Na+ GC’s open, Na+ rush in and raise voltage to +30 mV 5) D-repolarization initiated when Na+ GC’s close and K+ GC’s open; K+ rushes out returning interior to -70 mV, but an overshoot causes 6) E-hyperpolarization; Na/K pumps return interior to -70 mV

3. Refractory periods a. Time period when a threshold stimulus cannot initiate an AP

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b. Time during which not even a suprathreshold stimulus can trigger an AP is the absolute refractory period

1) Corresponds to when Na+ GC’s are first opened until near the return to the RP

c. Time during which only a suprathreshold stimulus can trigger an AP is the relative refractory period 1) Corresponds to the hyperpolarization period d. Because of refractory period, AP’s initiaited at axon hillock can only proceed forward, not back: AP travels from axon hillock to SEB

4. Saltatory conduction a. Unmyelinated axons conduct AP’s at ~ 1-2 m/sec; heavily myelinated axons conduct up to 120 m/sec: Why? b. Unmyelinated axons have Na+ & K+ GC’s evenly spaced along entire axon c. Myelinated axons have Na+ and K+ GC’s concentrated at nodes of Ranvier, about 1 mm apart d. Ionic flow, a very fast process, has ions diffusing a longer distance, faster 1) An AP in an unmyelnated axon is like taking small steps 2) An AP in a myelinated axon is like taking leaps (Saltate = jump) e. Myelin, a most lipid substance, inhibits diffusion of ions and is therefore more E efficient

5. Conduction speed a. Speed of an AP is not affected by the strength of the stimulus b. Speed is affected by:

1) Temperature-increased temperature increases molecular motion and therefore ions diffuse (ionic flow) faster 2) Presence of myelin 3) Fiber diameter-speed increases as fiber diameter increases; large diameter fibers simply have more room

c. Fiber types 1) Type A-heavily myelinated, large diameter, > 100 m/sec a) Sensory (somatic afferent) and somatic motor neurons 2) Type B-lightly myelinated, medium diameter, 20-30 m/sec a) White matter of CNS b) Preganglionic fibers of ANS 3) Type C-umyelinated, small diameter, 2 m/sec a) Gray matter of CNS b) Postganglionic neurons of ANS 6. The synapse: communication between neurons a. The AP cannot cross synaptic cleft, or space, found between two neurons b. Transmission is very similar to events at the myoneural junction

c. The first neuron sending AP is called the presynaptic neuron while the second neuron is called the postsynaptic neuron d. Membrane of SEB is referred to as the presynaptic membrane; membrane on postsynaptic neuron with receptors is the postsynaptic membrane

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e. Functions: 1) Regulates neural activity by excitation or inhibition 2) Synaptic connections allow learning 3) Allows a one-way conduction path 4) Site of action for many drugs f. Other kinds of junctions (all can be called synapses): myoneural and neuroglandular g. Types of synapses:

1) Electrical-cells communicate via gap jcts; no delay in speed at junction (embryonic neurons, smooth and cardiac muscles) 2) Chemical-communication uses neurotransmitters

h. Types of synapses: presynaptic & postsynaptic neurons 1) Axodendritic-axon of presynaptic neuron meets the dendrite of a postsynaptic neuron 2) Axosomatic-axon of presynaptic neuron meets the cell body (= soma) of a postsynaptic neuron 3) Axoaxonic-axon of presynaptic neuron meets the axon of a postsynaptic neuron; rarest of 3 kinds 4) Postsynaptic neurons might have from 8000 (CNS to motor neurons) to 100,000 (in the brain) presynaptic contacts!!!

i. Chemical synapses transmission 1) NT’s are made by neurons often from amino acids 2) NT’s are stored in synaptic vesicles located in SEB’s 3) NT’s are released when an influx of Ca++ arrive from synaptic cleft

4) Ca++ causes synaptic vesicles to move to presynaptic membrane and release NT’s by process of exocytosis 5) NT’s diffuse across the synaptic cleft and bind with receptors on postsynaptic membrane 6) Receptor is associated with chemically-sensitive GC’s 7) What kind of molecule does this GC respond to? An NT, a chemical 8) Gated channel classification:

a) Voltage-sensitive-these respond to voltage shifts and change conformation allowing ion flow b) Chemically-sensitive (Ligand)-these respond to chemicals, or NT’s. When a NT bonds to receptor site on this channel, it opens or leaks allowing ion movement c) Mechanically-sensitive-these change conformation in response to physical distortion of the membrane

9) Postsynaptic neuron responses a) When NT binds to receptor there are 2 possible actions: i. Excitatory (A & B) ii. Inhibitory (C & D)

b) A-If receptor causes a Na+ GC to open, this will allow Na+ IN and the effect will be excitatory

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c) B-If receptor causes both Na+ & K+ GC to open, the effect will still be excitatory (Na+ moves in much faster than K+ moves out) d) C-If receptor causes a K+ GC to open, this will allow K+ OUT and the effect will be inhibitory e) D-If receptor causes a Cl- GC to open, this will allow Cl- IN and the effect will be inhibitory

10) EPSP’s a) Makes the RP of the postsynaptic neuron LESS negative

b) Usually (probably never) a single presynaptic neuron carrying a single AP cannot initiate an AP in the postsynaptic neuron c) The change of potential from the RP towards threshold in a postsynaptic neuron is called an Excitatory PostSynaptic Potential or EPSP d) A & B are EPSPs e) Examples of NT’s that generate EPSP’s: Glutamate, aspartate, and ACh (usually)

11) Excitatory transmission issues: a) Synaptic delay-time for a message to cross the synaptic cleft using an NT 1) Time for NT release 2) Time for NT diffusion across synaptic cleft

3) Time for NT to activate receptor to generate AP in postsynaptic neuron

b) Synaptic fatigue-caused by presynaptic neurons firing in rapid succession that eventually depletes NT and ATP reserves c) Two mechanism by which synaptic transmission operates:

1) Causes chemically-sensitive Na+ GC to open (called the ionotropic effect) 2) Or, activates an EZ adenylate cyclase converting ATP to 3’5’ camp and (take Bio 202)

12) IPSP’s a) Makes the RP of the postsynaptic neuron MORE negative; hyperpolarizes the membrane b) The change of potential from the RP AWAY from threshold in a postsynaptic neuron is called an Inhibitory PostSynaptic Potential or IPSP c) Which 2 polarity changes in graph are classified as IPSP’s? C & D d) What were their causes? K+ or Cl- GC channels were opened e) Examples of NT’s that generate IPSP’s: glycine and GABA

j. Integration

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1) When a postsynaptic neuron is brought closer to threshold it is said to be facilitated; this occurs with the aide of many presynaptic neurons 2) Whether neuron fires depends on NET input of other presynaptic cells a) Typical EPSP has a voltage of 0.5 mV & lasts 20 msec b) Typical neuron would need 30 EPSP’s to reach threshold 3) EPSP’s can be summed, or added, together

a) Temporal summation occurs when a single presynaptic neuron fires in rapid succession causing the postsynaptic neuron to receive many EPSP’s in a short period of time b) Spatial summation occurs when many presynaptic neurons fire simultaneously (generating many EPSP’s) on a single postsynaptic neuron

4) Integration is the net sum of both EPSP’s and IPSP’s a) If # of EPSP’s > # of IPSP’s and the sum is < threshold à No AP is generated in the postsynaptic neuron (Postsynaptic neuron is said to be facilitated b) If # of EPSP’s > # IPSP’s and the sum is > threshold-à AP is generated in the postsynaptic neuron c) If # of IPSP’s > # EPSP’s -à No AP is generated in postsynaptic neuron (AP is blocked)

5) More synapses a neuron has the greater its information-processing capability a) Cells in cerebral cortex with 40,000 synapses b) Cerebral cortex estimated to contain 100 trillion synapses 6) Chemical synapses are decision-making components of NS-give ability to process, store, & recall information due to neural integration 7) Neural integration is based on types of postsynaptic potentials produced by NT’s

7. Types of NT’s a. 100+ NT’s in 3 major categories 1) ACh is formed from acetic acid and choline 2) Amino acid (aa) NT’s

3) Monoamines synthesized by replacing COOH (carboxyl) in aa’s with another functional group a) Catecholamines: epinephrine, norepinephrine, & dopamine b) Indolamines: serotonin & histamine

b. NT survey 1) ACh

a) Location of release: all myoneural jcts involving skeletal muscle, some smooth muscle, cardiac muscle, and in brain b) Synthesized from acetyl CoA and choline in neuron

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c) Broken down by EZ acetylcholinesterase (AChE) into acetate and choline d) Released in units called quanta (1000 to 10,000 molecules) e) Usual action: excitatory, except in cardiac muscle f) Synapses that involve the use of ACh are called cholinergic synapses; neurons that relase ACh at the SEB’s are called cholinergic neurons g) Drugs that affect ACh:

i. Curare: formed from SA tree resin; competitive inhibitor with ACh; used by natives on arrow heads and dart tips, in medicine for surgeries to relax muscles, & to treat muscle spasms in neurological disorders ii. Nerve gas/organophosphate pesticides: These inactivate AChE and cause spastic paralysis (continued state of muscle contractions) iii. Botulism toxin: inhibits release of ACh and causes flaccid paralysis (relaxation of muscles) iv. Nicotine: makes RP less negative by binding to ACh receptors (called nicotinic receptors) and increases Na+ leakage into postsynaptic neurons; no EZ exists for its removal v. Caffiene: Also makes RP less negative vi. Black Widow venom: Enhances release of ACh causing intense muscle cramps and spasms; also CNS problems vii. Tranquilizers: Varied action on many different NT’s, but all somehow make RP more negative

2) GABA a) Gamma AminoButyric Acid b) Usual action: Inhibitory c) Most common inhibitory NT in brain (~33% of neurons)

d) Works by opening Cl- channels and hyperpolarizes postsynaptic membrane e) Valium enhances GABA by binding to & opening GABA receptors f) Huntington’s chorea-hereditary disease that causes destruction of GABA and ACh-secreting neurons in brain g) Effects motor control (chorea = dance) and eventually causes dementia by age 40

3) Glycine a) Usual action: inhibitory b) Most common in spinal cord, but also found in brain & retina

c) Strychnine blocks glycine receptors causing spastic paralysis

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4) Norepinephrine (NE) a) Usual action: excitatory or inhibitory depending on location

b) Can be either because it uses secondary messenger mode of action (Bio 202) c) Released at some myoneural jcts and neuroglandular jcts associated with ANS; also in brain d) Excitatory for arousal, mood, and dreaming e) Amphetamines are chemical mimics

5) Dopamine (DP) a) Usual action: excitatory or inhibitory depending on location

b) Can be either because it uses secondary messenger mode of action (Bio 202) c) Released in many brain areas; especially high conc. in substantia nigra of midbrain (See brain section) d) Important in mood elevation, involuntary control of skeletal muscles e) Cerebral nuclei release DP that helps control subconscious movements of skeletal muscles; destruction of neurons that release causes Parkinson’s disease f) Cocaine inhibits DP removal from specific brain pleasure areas

6) Serotonin (ST) a) Usual action: usually inhibitory, but depends on location b) Released in many brain areas, but also retina, spinal cord

c) Important in mood, sleepiness, alertness, and thermoregulation d) Lowered levels often associated with chronic depression e) Prozac, Paxil, Zoloft inhibit reuptake of ST at SEB-ST stays in synapse longer f) Interactions among NE, ST, & other NT’s responsible for sleep-wake cycle g) LSD binds receptors and stops ST’s inhibitory effects

7) Neuropeptides a) Chains of 2 to 40 aa that modify actions of NT’s

b) Stored in axon terminals as larger secretory granules (called dense-core vesicles) c) May be released with NT or only under stronger stimulation d) Some released from nonneural tissue such as gut-brain peptides that cause food cravings e) Heroine and Morphine mimic

c. Cessation & modification of the signal 1) Mechanisms to turn off stimulation

a) Diffusion of NT away from synapse into ECF where astrocytes return it to the neurons

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b) Synaptic knob (SEB) reabsorbs aa and monoamines by endocytosis & breaks them down with monoamine oxidase c) AChE degrades ACh in synaptic cleft

2) Neuromodulators modify synaptic transmission a) raise or lower number of receptors b) Alter NT release, synthesis, or breakdown

c) Transmission is not simply the release of NT and binding to receptor; much more complex

d. Downregulation 1) Body attempts to maintain homeostasis 2) If too much NT released, this disrupts homeostasis

3) Postsynaptic neuron decreases manufacture of receptors, a process called downregulation, in an attempt to restore homeostasis 4) If too little NT released, postsynaptic neuron increases number of receptors called upregulation 5) What happens if a chemical mimic (an illegal drug) of an NT is introduced and affects your pleasure center? 6) Drug addiction a) Drug overstimulates pleasure center b) Postsynaptic neurons downregulate receptors

c) Normal levels of NT’s don’t stimulate pleasure center to same intensity d) What do you do? Take more of the drug e) Cycle is repeated until chemical dependency is developed f) This view is greatly oversimplified, but gives a general idea of one mechanism of drug addiction (Cocaine blocks DP reuptake channels and keeps DP in synaptic cleft longer)

8. Neuron regeneration a. At ~ 6 months, most nerve cells lose their mitotic apparatus

b. Neurons can repair if cell body remains intact, but level of repair varies depending on CNS or PNS c. PNS 1) After damage, Schwann cells multiply and form cellular cord 2) Axon distal to injury degenerates; nucleus activity increases

3) Several axon branches grow into cord created by Schwann cells; only one finds opening and reestablishes synaptic contact 4) Sometimes new axon bud wanders and never makes recontact 5) Diameter and speed of AP in new axon is reduced

d. CNS 1) Repairs are very limited because: a) More axons are usually involved b) Astrocytes produce scar tissue c) Astrocytes release inhibitory chemicals to axon growth

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d) Microglial are phagocytic and clean up debri and potentially beneficial materials for growth

9. Neuronal pools and circuits a. Statistics: 1) 107 sensory neurons 2) 1010 interneurons 3) 5 X 105 motor neurons b. Sensory neurons are organized into receptors or sensory organs c. Motor neurons are organized into motor units d. Interneurons are organized into neuronal pools

e. Neuronal pool is 1000’s to millions of interneurons that share a specific body function 1) Control rhythm of breathing 2) Contain both excitatory and inhibitory neurons 3) May affect action of neuronal pools f. Neuronal circuits

1) Simple series (serial) circuit-one neuron leads directly to next in linear sequence

a) Perhaps an ascending pathway transmitted info about pain to cerebral cortex

2) Divergent a) One cell synapses on others that each synapses on others

b) Single neuron starting in brain that stimulates many skeletal muscle cells to contract c) Sensory neuron bringing in info about pain to CNS-has to spread quickly

3) Convergent a) Several neurons synapse on the same postsynaptic neuron b) Gives strong excitation or inhibition

c) Diaphragm and rib muscles both under subconscious control, but can be consciously overridden when holding breath

4) Reverberating a) Neurons stimulate each other in linear sequence but one cell stimulates the one to start the process all over b) Longer lasting than other circuits; broken by fatigue or inhibitory impulses from another pool c) Breathing rate, coordinated muscle activities, wake-sleep cycle, & short-term memory

5) Parallel after-discharge a) Input neuron stimulates several pathways which stimulate the output neuron to go on firing for longer time after input has truly stopped b) Stream of impulses received by postsynaptic neuron

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c) Withdrawal reflex-you can remove your foot, shift balance, move arms, feel pain, and say “ouch” at same time

10. Diseases a. Alzheimer’s disease 1) 100,000 deaths/yr 2) 11% of population over 65; 47% by age 85 3) Symptoms:

a) Memory loss for recent events, moody, combative, lose ability to talk, walk, & eat b) After autopsy: i. Atrophy of gyri (folds) in cerebral cortex ii. Neurofibrillary tangles and senile plaques c) Degeneration of cholinergic neurons & deficiency of ACh and growth factors

4) Genetic connection confirmed for some forms b. Parkinson disease

1) Progressive loss of motor function beginning in 50’s or 60%-no recovery 2) Degeneration of dopamine-releasing neurons in substantia nigra 3) Prevent excessive activity in motor centers (Cerebral nuclei) 4) Involuntary muscle contractions: pill-rolling motion, facial rigidty, slurred speech, illegible handwriting, slow gait 5) Treatment is drugs and physical therapy a) DP precursor can cross blood-brain barrier b) Deprenyl (MAO inhibitor) slows neuronal degeneration c) Surgical technique to relieve tremors

BraiBrainn 1. Embryology

a. To understand brain structure, it is necessary to follow embryological development of NS b. A thickening along dorsal length of embryo (~17 days) called the neural plate gives rise to all neurons and most neuroglial cells c. Midline of plate invaginates to become neural groove; elevated sides are called neural folds d. Neural folds meet to form neural tube e. Most of PNS comes from neural folds f. Lumen of neural tube becomes central canal of the spinal cord and ventricles in the brain

1) Humans are chordates partly because they have a dorsal ‘hollow’ nerve cord

g. By 4th week of development, 3 swellings or primary vesicles have formed at anterior end; these are: 1) Forebrain or prosencephalon

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2) Midbrain or mesencephalon 3) Hindbrain or rhombencephalon h. By 5th week, there are 5 swellings or secondary vesicles

1) Prosencephalon divides into anterior telencephalon and posterior diencephalon 2) Mesencephalon remains undivided 3) Rhombencephalon divides into anterior metencephalon and posterior myelencephalon

i. These 5 embryological brain regions become many familiar brain parts later in development; these will be our 5 ‘boxes’ to help organize brain structure

j. The brainstem 1) Most of the 4 lower embryological brain regions make up the brainstem 2) Cerebellum is not considered part of brainstem

2. The brain: stats and general functions a. Probably the 3rd largest organ in body: 1300-1500 g; range = 750-2100 cc volume b. Cerebrum makes up 7/8 of total weight c. 100 billion neurons (10-15X more neuroglial cells d. High metabolic rate: 20% cardiac output at rest, but only 2% body wt e. General functions: 1) Coordinates and controls bodily functions 2) Memory, learning, intelligence 3) Instinctual behavior 4) Orientation of body parts

3. The brain: protection a. Skeletal aspects: enclosed by cranium b. Inside cranium are 3 membranes called meninges (singular meninx) c. From outermost to brain’s surface: Dura mater, arachnoid, pia mater d. Dura mater 1) Dura = tough; mater = mother

2) Double-layered: an outer periosteal layer that lines inner surface of cranial bones and an inner meningeal layer that adheres to brain’s surface 3) Fused over most of brain, but separates into dural sinuses; collecting area for venous blood and allows return to main circulation 4) Space below dura mater (meningeal layer) is the subdural space 5) Extensions of dura mater (dm) partition and support major brain parts: 2 cerebral hemispheres and cerebellum a) The 3 extensions of dm fill: i. Longitudinal fissue ii. Transverse fissure iii. Area between two cerebellar hemispheres

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e. Arachnoid 1) Net-like or web-like layer composed of fine filaments

2) Usually does not extend into fissures, but at spots penetrates dm and reaches dural sinuses forming arachnoid villi 3) Arachnoid villi allow CSF to be returned to main circulation 4) Space between filaments and below arachnoid and above pia mater is the subarachnoid space a) Filled with CSF

f. Pia mater 1) Delicate mother 2) Thin and contacts surface of brain 3) Modified areolar CT, highly vascular, and anchored by astrocytes 4) Nourish underlying cells

5) Along roofs of ventricles blood vessels from pia mater are part of choroid plexi 6) Capillaries from pia mater and ependymal cells form choroid plexus 7) Choroid plexi secrete CSF 8) Meningitis-inflammation of meninges usually caused by bacteria or viral infections (does not usually affect dm)

g. Cerebrospinal fluid (CSF) 1) ~ 800 ml produced each day and 140-200 ml baths CNS 2) Higher in Na+, Cl-, Mg++, and H+; lower in Ca++, K+, & glucose

3) Circulates through subarachnoid space and ventricles of brain and the central canal and subarachnoid space of the spinal cord 4) Formed by choroid plexi in ventricle roofs and reabsorbed by arachnoid villi in dural sinuses 5) Properties/functions:

a) Lymph-like fluid forming a protective cushion around brain and spinal cord b) Specific gravity of 1.007 suspending brain in a watery environment c) Blows to head are spread over wide area d) Transports nutrients and chemical messengers and remove wastes e) Creates a chemically stable environment around neurons of brain

6) Hydrocephalus-abnormal accumulation of CSF in the brain caused by some sort of blockage in ducts a) Treated with a shunt

h. Blood-brain barrier (BBB) 1) 3 main parts: a) Capillaries with tight jcts b) Thick basement membranes c) Astrocytes

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2) Functions: a) Selective filtration of blood to brain b) Maintains a chemically stable environment around brain c) Prevents easy access to brain for bacteria and viruses

3) Substances that pass across: water, oxygen, carbon dioxide, glucose, & lipid-soluble substances (aa, alcohol, caffeine, anesthetics 4) Substances excluded: proteins, large lipids, creatinine, urea, toxins, & antibiotics 5) Circumventricular organs (CVO’s): areas of brain (around 3rd & 4th ventricles) not protected by BBB a) Hypothalamus

4. Ventricles a. Lateral ventricles (1st & 2nd) within each cerebral hemisphere 1) Connect to 3rd ventricle by the interventricular foramina b. Third ventricle-forms midplane of diencephalon 1) Connect to 4th ventricle by cerebral (= mesencephalic) aqueduct c. Fourth ventricle-mostly between pons and cerebellum 1) Connect to spinal cord through central canal 5. Telencephalon

a. Composed of 2 hemispheres (right & left) divided into 5 lobes: frontal, parietal, occipital, temporal, insula

b. Fissures: 1) Deep indentation that separates cerebellum from both cerebral hemispheres is transverse fissure 2) Deep indentation that separates cerebral hemispheres is longitudinal fissue

c. Surface features: 1) Sulci (sulcus) a) Shallow indentations (grooves) b) Central sulcus separates frontal from parietal lobes

c) Lateral sulcus separates temporal lobe mostly from frontal lobe

2) Gyri (Gyrus) a) Elevated ridges on brain’s surface

b) Precentral gyrus is raised area immediatelt anterior to central sulcus c) Postcentral gyrus is raised area immediately posterior to central sulcus

3) Many other sulci & gyri are recognized and have specific names, but these 4 are very prominent

d. Cross-sectional view through cerebrum reveals 3 layers/areas: 1) Cerebral cortex-outer 2-4 mm thick of gray matter 2) White matter-communication fibers

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3) Cerebral nuclei (= basal ganglia)-islands of gray matter within white matter

e. Cerebral cortex 1) Lobe names are based mostly on the bones they reside under 2) 5 lobes, 4 superficial

3) Gyri/sulci provide increased surface area for this highly important area of gray matter 4) Surface layer of gray matter ~ 3 mm thick a) Neocortex(6 layered tissue) i. Newest part of cortex ii. Layers vary in thickness in different regions of brain b) 2 types of cells: i. Satellite cells have dendrites projecting in all directions

ii. Pyramidal cells have an axon that passes out of area all the way to spinal cord

5) Frontal lobe a) Located beneath frontal bone; anteriormost lobe b) Primary Motor cortex (Brodmann’s #4) i. Located in precentral gyrus

ii. Pyramidal cells orginate here forming corticospinal (pyramidal) tracts where axons descend from cerebral cortex directly to the spinal cord w/o synapsing iii. Where we exert conscious control over our skeletal muscles iv. Innervation to body parts is proportional to motor units, not muscle size; (more area of primary motor cortex is dedicated to fingers than to thighs)

c) Premotor cortex (6) i. Immediately in front of precentral gyrus

ii. Learned repetitious motor skills; typing, playing a musical instrument, a sport, etc.

d) Broca’s area (44) i. Usually left hemisphere; superior to lateral sulcus at lower end of premotor area ii. Motor speech area iii. Coordinates skeletal muscle of larynx & pharynx with respiratory muscles

e) Prefrontal cortex (9, 10, & 45) i. Anterior to premotor cortex

ii. Functions: receives info from other lobes and integrates; abstract ideas, judgment, conscience; thought, intelligence, learning, motivation, personality; timeline of events iii. Slow development in children

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iv. Tumors in this area damage a person’s ability to reason v. Prefrontal lobotomy in 30’s & 40’s severed connections to rest of brain-cured very violent behaviors, but person had no concern about decorum

6) Parietal lobes a) Somatosensory cortex (1, 2, & 3) i. Located in postcentral gyrus

ii. Primary somatosensory area is where sensory stmuli (touch, pressure, pain, vibration, temperature, and receptors in muscles through body) are localized iii. Sensory neurons synapse in thalamus before reaching this area (allows thalamus to filter) iv. Other functions: integration & interpretation of sensory info; interprets textures & shapes; retrieves autobiographical memories v. Demonstrates that the area of cortex dedicated to sensations of various body parts is proportional to how sensitive that part of the body is and # motor units dedicated to an area

7) Temporal lobes a) Located below lateral sulcus beneath temporal bone

b) Wernick’s area (22): receives information from auditory & visual centers which allows comprehension of spoken & written language i. Usually left hemisphere c) Other functions: i. Auditory centers-where we hear ii. Interpretation of some sensory info iii. Storage of auditory (& visual) memories d) Gustatory cortex-taste

8) Occipital lobes a) Posteriomost lobes beneath occipital bone; no distinct separation from parietal lobes b) Primary visual cortex-where we see c) Visual association areas-interpretation of visual info d) Directs & focuses eyes (also frontal lobe)

9) Insula a) Deep lobes; access is through lateral sulcus b) Functions: i. Mostly unknown, but--- ii. Involved in taste and hearing iii. Interpreting sensory info from visceral receptors

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iv. Especially active when people look at pictures of their own faces

10) Cerebral lateralization a) Left hemisphere is categorical hemisphere: specialized for spoken & written language, sequential & analytical reasonal (math & science), analyze data in linear way b) Right hemisphere is representational hemisphere: perceives information more holistically, perception of spatial relationships, pattern, comparison of special senses, imagination & insight, music and artistic skills c) Highly correlated with handedness: 91% of people right-handed with left side categorical d) Lateralization develops with age: trauma more problems in males since females have communication between hemisphere (corpus callosum is thicker posteriorly)

11) EEG a) Electroencephalogram records voltage changes from postsynaptic potentials in cerebral cortex (graphical recording of the brain’s electrical activity) b) Differences in amplitude & frequency distinguish 4 types of brain waves

f. Tracts of cerebral white matter 1) Most volume of cerebrum is white matter 2) Types of tracts:

a) Projection-extend vertically from brain to spinal cord forming internal capsule b) Commissural-cross from one hemisphere to the other i. Corpus callosum is wide band of white fiber tracts ii. Anterior & posterior commissures are pencil-lead sized c) Association-connect lobes & gyri of each hemisphere to each other

g. Cerebral nuclei (= Basal ganglia) 1) Masses of gray matter deep to cerebral cortex

2) Receives input from substantia nigra and motor cortex & send signals back to these regions 3) Functions:

a) Involved in subconscious motor control & inhibition of tremors b) Regulates muscle tone for intention movements c) Reaching for object requires several conscious actions, but also subconscious contractions/relaxations of shoulder muscles d) Arm-swinging during walking

4) Parkinson’s disease

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6. Diencephalon a. Almost completely surrounded by cerebral hemispheres b. Third ventricle forms midplane c. Divided into 3 regions:

1) Thalamus-ovoid mass of gray matter protruding into lateral ventricle 2) Hypothalmus-below thalamus forming floor of 3rd ventricle 3) Epithalmus-superior portion of diencephalon; root over 3rd ventricle

d. Thalamus 1) ~80% of diencephalon 2) Paired-sometimes 70% fused in midline 3) Functions: a) Gateway to cerebral cortex

b) Receives nearly all (except smell) sensory info on its way to cerebral cortex c) Crude awareness of sensory info, but cannot localize d) Integrates & relays info to appropriate area e) Interconnected to Limbic system so is involved in emotional & memory functions

e. Hypothalamus 1) Below thalamus

2) Ventral borders: from optic chiasma to and including mammillary bodies 3) Several masses of nuclei: a) ANS control center: i. Cardiovascular regulation ii. Thermoregulation (thermostat) iii. Food & water intake (hunger & satiety centers) iv. Sleep & circadium rhythms

v. Subconsious control of specific muscle groups like facial expressions of rage vi. Sexual response-orgasm vii. Emotions: anger, fear, pain, pleasure viii. Endocrine functions: controls release of hormones from pituitary and makes own hormones ix. Mammillary bodies: memory, swallowing, and licking reflexes

f. Epithalamus 1) Superior portion of diencephalon; forms roof of 3rd ventricle 2) Inside lining of root has choroid plexus 3) Main structure is pineal gland (= epiphysis cerebri)

a) Cone-shaped mass (pine cone) extends from posterior end of epithalamus

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b) Neuroendocrine function-secretes melatonin that regulates circadium rhythms and reproductive cycles in lower vertebrates

i. Receives sensory neurons from optic nerve in mammals ii. Has pineal eye in reptiles

c) Has calcium carbonate crystals called brain sand g. Pituitary gland (= hypophysis cerebri) 1) 1.5 cm and 1 g

2) Inferior (ventral) to diencephalon and attached by a stalk called infundibulum 3) Resides in sella turcica of sphenoid bone 4) Endocrine function 5) Two part gland: a) Anterior pituitary (adenohypophysis) b) Posterior pituitary (neurohypophysis)

7. Mesencephalon: Midbrain a. Part of brainstem above (superior) diencephalon and below (inferior) metencephalon b. Cerebral aqueduct runs through c. CN III and IV for eye movements come off here d. Cerebral peduncles are bulges on anterior surface that hold pyramidal tracts e. Tegmentum connects to cerebellum & helps with fine motor actions through red nucleus f. Substantia nigra sends inhibitory signal to cerebral nuclei & thalamus (degeneration leads to tremors and Parkinson’s disease) g. Dorsal surface has 4 rounded bodies (each housing a nucleus) called the corpora quadrigemina

1) Superior colliculi-2 upper bodies functioning in tracking moving objects with your head and eyes 2) Inferior colliculi-2 lower bodies functioning in auditory reflexes such as turning head to a loud sound

8. Metencephalon a. Composed of 2 main parts: pons & cerebellum b. Pons 1) White fiber tracts run in two planes (directions)

a) Transverse-on surface of pons that connect two cerebellar hemispheres through middle cerebellar peduncles b) Longitudinal-underneath transverse and contain motor & sensory tracts connecting medulla with midbrain

2) Nuclei concerned with sleep, hearing, balance, taste, eye movements, facial expression, facial sensation, respiration, swallowing, bladder control, & posture a) Cranial nerves V, VI, VII, & VIII

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b) Respiratory centers: i. Apneustic ii. Pneumotaxic

c. Cerebellum 1) Little brain 2) Separated from cerebrum by transverse fissure a) Fissure filled with tentorium cerebelli 3) Two hemispheres (R & L) with a midsection called the vermis

4) In midsaggital section, an outer area of gray matter called the cerebellar cortex and an inner highly branched area of white matter called the arbor vitae, are observed a) Outer cortex is folded into folia

b) Cortex houses Purkinje cells-highly branched with as many as 200,000 synapses

5) Cerebellar peduncles (cp) a) Superior cp-connect cerebellum with midbrain and eventually motor areas of cerebral cortex b) Middle cp-(= surface transverse tracts) connect R & L hemispheres of cerebellum and to cerebral cortex c) Inferior cp-connects cerebellum to medulla & spinal cord

6) Functions of cerebellum: a) Coordinates skeletal muscle activities by selecting specific motor units (defects cause ataxia-jerky & uncoordinated movements) b) Cerebellum helps learn motor skills c) Maintenance of posture and muscle tone via sensory information from proprioceptors d) Judging passage of time e) Some memory functions f) Output: smoothes muscle contractions, maintains muscle tone & posture, coordinates motions of different joints, aids in learning motor skills, & coordinates eye movements

9. Myelencephalon: medulla oblongata a. 3 cm extension of brainstem and most inferior part of brainstem b. Houses ascending & descending nerve tracts 1) Pyramids on anterior surface are bulges of corticospinal tracts.

a) Cell bodies are found in cerebral cortex (primary & premotor cortexes) b) Decussation of pyramids-area where corticospinal tracts crossover to opposite side; therefore stroke victims usually have paralysis on opposite (contralateral) side of body from affected hemisphere

2) Olive-enlargement on lateral surface; relay center for info headed to cerebellum from spinal cord

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3) Internal gray matter houses many nuclei: a) Nuclei of sensory & motor cranial nerves: IX, X, XI, XII) b) Cardiac center adjust rate & force of heart beat c) Vasomotor center adjusts blood vessel diameter d) Respiratory centers control rate & depth of breathing

e) Reflex centers for coughing, sneezing, gagging, swallowing, vomiting, salivation, sweating, movements of tongue & head f) Fasciculus cuneatus/gracilis-posterior tract of spinal cord containing sensory info

10. Reticular formation a. Clusters of gray matter scattered throughout pons, midbrain, & medulla b. Regulates balance & posture 1) Relays information from eyes & ears to cerebellum 2) Gaze centers allow you to track moving objects c. Includes cardiac & vasomotor centers d. Origin of descending analgesic (pain) pathways e. Regulates sleep & conscious attention; injury leads to irreversible coma 11. Limbic system a. Loop of cortical structures surrounding deep brain b. Amygdala, hippocampus, fornix & cingulated gyrus

c. Amygdala important in emotions and hippocampus in memory; rest are unsure d. Memory

1) Information management requires learning, memory, & forgetting (eliminating trivia) 2) Hippocampus is important in organizing sensory & cognitive information into a memory; lesions here cause inability to form new memories 3) Amygdala important in emotional memories

e. Limbic system is sometimes called “emotional brain” f. Emotion

1) Prefrontal cortex controls how emotions are expressed (seat of judgment) 2) Emotions form in hypothalamus & amygdala

a) Artificial stimulation produces fear, anger, pleasure, love, parental affection, etc b) Electrode in median forebrain bundle in rats (or likely humans) and a foot pedal cause a rat to press pedal all day to the exclusion of food (quiet relaxes feelings in humans)

3) Much of our behavior is learned by rewards and punishments or responses of others to them

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Spinal CordSpinal Cord 1. Protection & coverings a. Location in vertebral canal of vertebral column b. Also protected by same 3 meninges, CSF, and vertebral ligaments c. Inside bone we find: 1) Epidural space 2) Dura matter 3) Subdural space 4) Arachnoid 5) Subarachnoid space 6) Pia mater d. Meningial modification:

1) Epidural space-space between wall of vertebral canal and dura mater

a) Filled with blood vessels, adipose, and loose areolar CT b) Site for injection for anesthetics (an epidural) 2) Dura mater of cord is continuous with dm of brain

3) A spinal tap remove CSF between L3 and L4 for diagnoses of infections, back pain, headaches, disc problems, and some strokes 4) Pia mater has lateral membranous extensions called denticulate ligaments, laterally stabilizing spinal cord

2. Gross anatomy a. Shape: cylindrical, slightly flattened anteriorly and posteriorly b. Length: 18 in (45 cm); 0.55 in (14 mm) diameter c. Enlargements:

1) Cervical enlargement supplies nerves to shoulder girdles and upper limbs 2) Lumbar enlargement supplies nerves to pelvic girdles and lower limbs

d. Inferior end (below lumbar enlargment) of cord tapers into a cone-shaped structure called conus medullaris (= medullary cone) e. A slender strand of fibrous CT anchoring conus medullaris to 2nd sacral vertebra is the filum terminale (attaches to coccyx); provides longitudinal stability of cord f. Mass of nerves (roots) arising from inferior cord exit together and run parallel-called cauda equina (resembles horse’s tail) g. Spinal cord has 31 pairs of spinal nerves

3. Spinal cord: XS anatomy a. Divided into R & L sides by: 1) Anterior median fissure 2) Posterior median sulcus

b. Outer area is white matter surrounding a butterfly or H-shaped internal gray matter

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c. White matter is composed of columns (funiculi) housing ascending/descending tracts 1) Anterior (= ventral) white column 2) Posterior (= dorsal) white column 3) Lateral white column d. Gray matter is organized into horns: 1) Anterior (=ventral) gray horn 2) Posterior (= dorsal) gray horn 3) Lateral gray horn 4) Many nuclei found in these e. Spinal cord terminology

1) Gray matter-composed of cell bodies and unmyelinated neuron parts; forms a ‘H’ or ‘butterfly’ shape inside white matter a) Horizontal bar of H is the gray commissure 2) White matter-composed of myelinated neuron parts; surround gray matter; also conducts information up and down spinal cord 3) Central canal-space in center of gray commissure that housesCSF and is the “hollow” in the dorsal hollow nerve cord of Chordates 4) Dorsal root-houses incoming sensory neurons 5) Dorsal root ganglion-houses cell bodies of sensory neurons 6) Ventral root-houses outgoing motor neurons 7) Spinal nerves-31 pairs along spinal cord; these are both sensory & motor

4. Spinal cord functions: a. Impulse conduction-conduit for ascending & descending information

1) Conveys sensory impulses from spinal cord to brain (ascending or sensory tracts) 2) Conveys motor impulses from brain to spinal cord (descending or motor tracts)

b. Reflex center c. Homeostasis 5. Impulse conduction a. Tract names indicate: 1) White column in which tract is located 2) Where cell bodies originate 3) Where axons terminate b. Principle tracts ascending (sensory) 1) Anterior spinothalamic a) Tract is found in anterior white colum b) Cell bodies originate in the spinal cord (spino) c) Axons terminate in the thalamus d) Conveys sensations of crude touch/pressure to thalamus 2) Lateral spinothalamus a) Tract is found in lateral white colume

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b) Cell bodies originate in the spinal cord (spino) c) Axons terminate in the thalamus d) Conveys sensations of crude pain/temperature to thalamus 3) Posterior spinocerebellar

a) Subconscious proprioception from one side; use of inferior cerebellar peduncle

4) Anterior spinocerebellar a) Subconscious proprioception from both sides giving position of muscles, joints, tendons; uses superior cerebellar peduncle

5) Fasciculus cuneatus/gracilis a) Posterior tracts conveying info for 2 pt discrimination, conscious proprioception, sterognosis, weight discrinimation, and vibration b) Recently discovered that pain from visceral organs conveyed here

c. Principle tracts descending (motor) 1) Lateral corticospinal a) Tract is found in lateral white column b) Cell bodies originate in the cerebral cortex (cortico) c) Axons terminate in the spinal cord d) Coordinates precise, discrete movements e) Seen as cerebral peduncles in midbrain

f) Forms pyramids in medulla (85% crossover in decussation region)

2) Anterior corticospinal a) Tract is found in anterior white column b) Cell bodies originate in the cerebral cortex (cortico) c) Axons terminate in the spinal cord d) Coordinates gross movements of axial skeleton e) Seen as cerebral peduncles in midbrain

f) Forms pyramids in medulla (do not crossover) 3) Medial/lateral pathways: rubrospinal, tectospinal a) Most other motor tracts originate in brainstem b) These are polysynaptic and controlled by cerebellum c) Divided into medial and lateral pathways

d) Medial pathways: Tectospinal, reticulospinal, & vestibulospinal tracts maintains posture & balance and provides reflex movements of head e) Lateral pathways: rubrospinal-precise movements of distal limb muscles i. Pathway originates in red nucleus of midbrain

6. Reflex center: How do neurons interact to cause a behavior? a. One way to understand how neurons interact to cause a behavior is by studying a reflex arc

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b. Reflex-an automatic, stereotypic, response to a stimulus 1) Automatic-an involuntary response

2) Stereotypic-response is repeated in similar fashion every time the correct stimulus is given

c. Reflex arc components 1) Receptors-detects a stimulus 2) Sensory neuron-brings sensory info from receptors to CNS

3) Center-CNS (brain & spinal cord) processes incoming sensory info and initiates a response 4) Motor neuron-carries info from CNS to an effector 5) Effector-a muscle or gland that executes response

d. Spinal cord gray matter/ dorsal root ganglion 1) Dorsal root ganglion (DRG)-location for cell bodies belonging to incoming sensory neurons 2) Dorsal (posterior) gray horn-mostly axons and some cell bodies of interneurons; structurally very thin 3) Lateral gray horn-mostly cell bodies of ANS preganglionic neurons 4) Ventral (anterior) gray horn-mostly cell bodies of motor neurons going to skeletal muscle

e. Two reflexes studied in detail: stretch & tendon reflexes; In less detail the cross-extensor and withdrawal reflexes f. Stretch reflex: neural circuit 1) Receptor is a muscle spindle sensitive to stretch (the stimulus)

a) Sense organ that monitor the length of skeletal muscles are proprioceptors b) 4 to 10 mm long modified skeletal muscle cells c) Intrafusal fibers that respond to gamma motor neurons & are wrapped with afferent fibers that respond to stretch

2) When patellar ligament is struck with mallet, the quadriceps (front thigh) muscles are stretched 3) Sensory neuron transmits nerve AP’s to spinal cord where sensory neuron branches into 3 axon collaterals: a) First axon collateral synapses directly with a motor neuron

i. This motor neuron returns to muscle being stretched (the quads) and initiates a contraction (contraction of quads = kick) ii. Contraction also shortens the muscle and counteracts the stretch iii. It is this collateral that makes a stretch reflex monosynaptic (involving only 1 synapse) and therefore fast (less synaptic delay)

b) 2nd axon collateral i. Synapses with and excites an interneuron ii. This interneuron inhibits a motor neuron

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iii. This motor neuron WOULD take AP’s to the hamstrings

iv. Prevents hamstrings from contracting at same time as quads

c) 3rd axon collateral synapses with an interneuron (an ascending sensory neuron) taking AP’s to the brain

4) Final comments on stretch reflex a) Monosynaptic-since there is only one synapse between sensory & motor neurons, the response (the kick) to the stimulus (the stretch) is very quick b) Ipsilateral-note that entire circuitry is on one side of the spinal cord; if stimulus occurs to your R patellar tendon, the R leg kicks c) Reciprocal innervation-note that when the quadriceps was excited, the antagonist, or hamstrings in this case, was inhibited d) Neurological significance-a simple test for proper functioning of neurons; any observable delay in kick could indicate a number of different neurological or even metabolic disorders

g. Tendon reflex: neural circuit 1) Receptor is a Golgi tendon organ sensitive to tension (the stimulus)

a) Located in each tendon; prevents muscle from over contracting b) Proprioceptors in a tendon near its jct with a muscle – 1 mm long; an encapsulated nerve bundle c) Excessive tension on tendon inhibits motor neuron; muscle contraction decreases d) Also functions when muscle contracts unevenly

2) Polysynaptic and ipsilateral 3) If excessive tension occurs, a sensory neuron transmits nerve AP’s to spinal cord where sensory neuron branches into 3 axon collaterals:

a) First axon collateral synapses directly with and excites an interneuron

i. This interneuron synapses with and inhibits a motor neuron returning to the muscle building tension ii. Lowers stimulation of overcontracting muscle iii. Since an interneuron is involved in the pathway, 2 synapses are present making this reflex polysynaptic

b) 2nd axon collateral i. Synapses with and excites an interneuron

ii. This interneuron excites a motor neuron going to antagonist of muscle building too much tension iii. Antagonist contracts which lengthens muscle that is too short iv. This is reciprocal innervation

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c) 3rd axon collateral synapses with an interneuron (an ascending sensory neuron) taking AP’s to the brain

4) Final comments on tendon reflex a) Tendon reflexes maintain posture and protects tendons from too much applied force

h. Withdrawal/Cross extensor reflexes 1) Both are polysynaptic and intersegmental 2) Withdrawal is ipsilateral; cross extensor is contralateral 3) Withdrawal reflex is a response to a harmful (noxious) stimulus

4) Cross extensor is associated with withdrawal reflex, but helps maintain balance 5) Flexor (withdrawal) reflex is withdrawal of foot from nail 6) Cross extensor reflex is maintaining balance by extending other leg