Physio - Neuro - Review - Stacey Trent - 2005

7/29/2019 Physio - Neuro - Review - Stacey Trent - 2005

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CNS

PhysiologyReview


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Electrophysiology

Length constant - distance along

membrane at which voltage signal is

reduced to 37% of its original amplitude Time constant - amount of time it takes

to reach 63% of membrane steady-state

voltage


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Electrophysiology

Temporal Summation - determined by

time constant - larger the time constant of

postsynaptic cell, the longer it lasts and the greaterthe extent of temporal summation

Spatial Summation - determined bylength constant - larger the length constant, themore potent the potential when it reaches axon

hilloc (more efficient electronic conduction)


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Metabolic & Circulatory

Features Gases, water, small MW compounds &

lipid-soluble molecules can diffuse

across BBB High MW compounds and polar

molecules can NOT diffuse across BBB

Glucose, amino acids, pyruvate,ketones, etc. cross via active transport


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Features Capillary endothelium = BBB (glia surround

endothelium)

BBB can be breached by using ahyperosmotic sucrose solution to shrinkendothelial cells and loosen the tight

junctions

Smoking is also an effective method ofbreaching BBB (~20% blood in lungs goesstraight to brain)


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Features Monro-Kellie Doctrine - an increase in any

component in calvarium (tumor, edema, CSFblockage) must be accompanied by a decrease

in another component Cytotoxic edema - intracellular edema caused by

ischemia - ion pumps shut off and cells swell -BBB intact

Vasogenic edema - extracellular edema causedby hemorrhage - BBB permeability increased

Both types of edema lead to cell death


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Features Mean cerebral blood flow doesnt vary with

BP under normal circumstances

When blood flow does change, it changes inrelation to metabolism (lots of active pumps -

lots of energy needed)

Exception - Hypercapnia!!! - when pCO2

increases, BP increase


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Features Deoxyglucose - passes through glucose pumps but

isnt metabolized

PET scan - uses flourodeoxyglucose (F18) probe -

high energy radioactive material with short T1/2 - moremetabolically active cells take up more F18 - imagesenergy utilization

SPECT scan - uses lipid soluble probe (HMPAO) w/longer T

1/2than F

18- diffuses across cell then is

demethylated (trapped) - measures blood flow

fMRI - uses blood oxygen dependent level (BOLD)contrast - detects oxygenated vs. deoxygenated Hb -

activity measured by deoxyHb replacing oxyHb


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NeurotransmittersName Effect Synthesis Degradation Location

GABA Inhibitory GAD fromGlutamate

Transported,GABA-T (PLP)

Ubiquitous

Glutamate Excitatory Gluatminase,

other

Transported Ubiquitous

Acetylcholine Excitatory Choline,

acCoA, CAT

AchE - choline

to pre

Basal Foreb.

Hippocampus

Epi, NE, DA Excitatory

(except a1)Tyrosine, TH Trans intact

COMT

NE- LC

Epi -brainstem

DA- SN, Stri.

Serotonin

(5-HT)

Excitatory Tryptophan,TH

Trans thenMAO break

Pons Raphe

Histamine Excitatory Histidine,

(Decarboxyl)

Transferase,

MAO

Hypothalamus

Peptides Both Precursors Proteases Ubiquitous


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Glutamine Glutamate GABA

GLU and GABA Synthesis

Glu GABA utilizes cofactor PLP Deficiencies in B6 lead to inhibited

GABA synthesis causing convulsions

(decreased inhibition) Thiazide diuretics can be a cause of B6

deficiency

PLP


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Acetylcholine Synthesis

ACh synthesis is substrate limited

(ie dependent on the [choline])

Uptake of choline is regulated making it hard

to increase Ach (instead drugs are used toinhibit the breakdown of Ach)

Choline + Acetyl CoA ACh


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Catecholamine Synthesis

Limited by [tyrosine]

Regulated by end product inhibition oftyrosine hydroxylase

Tyrosine hydroxylase is also dependent upon

tetrahydrobiopterin (THB) - when TH isphosphorylated, its affinity for THB increases

Epi synthesis utilizes SAM to get methylgroup (corticosteroids upregulate this)

Tyrosine DOPA Dopamine NE EPITH


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More NT Synthesis

Serotonin Synthesis Limited by [tryptophan]

Insulin increases the transcription of transportersthat selectively uptake Phe and Tyr as oppose toTrp such that Trp is more available in the blood

Melatonin Synthesis Breakdown product of serotonin

Activated by darkness

Neuropeptides Regulated by gene transcription


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NT Release

Electrical Aspects

Ca+2 dependent - amount of Ca+2 released proportional toNT release

Tetrotoxin - blocks Na+ channels - blocks presynapticactivity - no Ca+2 released - no vesicles released

K+ channels are poisoned - sustained release b/c cantrestore RMP

Molecular Aspects

Synapsin brings vesciles to the membrane

Ca+2 phosphorylates synapsin releasing the vesicle

SNAREs & SNAPs aid in vesicle fusion


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NT Receptors

Ach

Nicotinic

Cation Channel (Ca++

in CNS) Spinal Cord, Sup. Colliculus

Muscarinic G-protein-coupled, Gi inactivates Adenylate

Cyclase, Gq activates PLC- Ca++

influx M1- striatum, hippocampus, cerebrum

M2- cerebellum


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NT Receptors

GABA

GABAA

Postsynaptic Cl- channel - reinforces the RMP

Agonists- inhibition. Prevents NT release

Muscimol, Barbs, (Benzos) GABAB

G-protein-coupled, activates Adenylate Cyclase

Axoaxonal

PRE

POST GABAA

GABAB

-

-


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Somatosensory

Mechanoreceptors (Ab afferents) MOA: pressure stretches membrane and opens Na+

channels causing Na+ to flow into cell

Stimulus intensity is proportional to receptorpotential

Coded by frequency of firing

Slow Adapting - Touch and Pressure - prolonged stim

Merkels Disk - detect location of stimulus

Ruffini Corpuscles

Fast Adapting - Touch - onset/offset stim

Meissners - detect low-freq. vibrations or flutter

Pacinian Corp. - detect high frequency -

Hair follicle - velocity detector

Proprioception Muscle spindles - detect length

Joint receptors - detect position, direction & velocity ofmovement


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Somatosensory

Afferent Fiber Types Ia > Ib > II = Ab > A > C All proportional to fiber diameter

In general, deeper the receptor in the skin thelarger the receptor field

DCML 1 - skin to dorsal horn up gracile or cuneate

fascile to medulla 2 - up ML to thalamus to synapse VPL or VPM 3 - up post. IC to synapse in somatosensory

cortex (312)


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Somatosensory

Pain Detected by nociceptors (free nerve endings)

Prolonged or repetitive activation of pain receptorsmakes them more sensitive

Pain response Sensory - detected by nociceptors

Behavioral - active, passive or nonavoidance

Autonomic - severe pain (SNS response) vs.visceral pain (PSNS response)

Motor - w/drawl or guarding (visceral)


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Pain - Receptor Specificity

Nociceptors - detect mechanical, heat orchemical stimulation Fast (1st) pain - A fiber - smallest mylenated fiber

that senses localized pain or heat > 45C

Slow (2nd) pain - C fiber - unmylenated thatsenses poorly localized pain

More C fibers than A fibers C fiber response outlasts stimulus

Thermoreceptors - detect temp < 45C Cold (A & C) Warm (C)

Itch Receptors (C)

Activated by histamine


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Physiology of Pain

Damage to cell releases K+ whichdepolarizes cell and activates nociceptorleading to release of substance P and CGRP(calcitonin gene related peptide).

Substance P acts on mast cells to evokedegranulation causing release of histaminepotentiating the nociceptor.

CGRP dilates blood vessels causing edemaand release of bradykinin further potentiatingnociceptor


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Somatosensory

Spinothalamic System (ALS) - fast pain

- 1 Ab fibers synapse on lamina V dentrites

in lamina IV and are inhibitory (massageinhibition)

Spinoreticular System - slow pain

Spinomesencephalic - emotional &autonomic affects of pain


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Axon Reflex

Mediated by C fibers

W/in 30 sec, C fibers transmit signal back out to

periphery causing release of substance P which

dilates blood vessels leading to red flare

p

pp

Type C

Triple response:

1) Red rxn - from

direct stim - from

bleeding/dilation

2) Wheal - fromincreased

histamine &

capillary

permeability -

edema

3) Red flare - axon

reflex (subP)


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Somatosensory

Nociceptive Fibers (A orC)synapse on SC neurons in

the anterior horn (A).

Descending 5-HT or NEneurons can modulate these

synapses to prevent pain

transmission.

Lesions in any part of thedescending pathway will

cause temporary

hyperalgesia


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Auditory Physiology Sensory Transduction

Movement of basilar membrane causes deflection ofstereocilia against tectorial membrane

Deflection toward tallest stereocilia causes K+ channels toopen (depol)

Endolymph - high in K+

Depolarization opens Ca+2 channels releasing NTs andopening Ca+2-dependent K+ channels causing K+ to flowback out and repolarize the hair cell

Perilymph - low in K+

Pitch Perception

Location of highest amplitude deflection on basilarmembrane is factor for coding pitch

Each hair cell is tuned to a resonance frequency

Electrical tuning - placement along basilar membrane

Mechanical tuning - stiffness/flacidness of hair cell - (stiffer nearbase)


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Auditory Physiology

Hair Cells Inner Hair Cells

short, stiff stereocilia

Receive more afferents - predominant role in transfer ofauditory info to CNS

Outer Hair Cells Receive input from CNS that can change membrane

potential (change amplitude)

Efferents to OHCs release ACh onto OHCs hyperpolarizingthem and decreasing their motor output causingsuppression of sensory response and elevating auditorythreshold


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Neural Coding of Pitch

Phase locking - @ lower frequencies (


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A lesion above what level of

the auditory pathway will

result in problems localizingsound?


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Answer:

Superior Olivary Nucleus 1- spiral ganglion to cochlear nucleus

2- info to both superior olivary nuclei

1st binaural input

3- inferior colliculus

4- medial geniculate nucleus (thalamic relay)

5- primary auditory cortex on superiortemporal gyrus (41 & 42)


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Auditory Physiology

Perception of Loudness

Depends both on amplitude and frequency b/c

minimum sound intensity varies with frequency of

sound (Equal Loudness Contours)

Sound Localization

Loudness difference between the two ears is

detected by the LSO (high freq) Phase difference between the two ears is detected

by the MSO (low freq)


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Vestibular System

Hair cells - similar to those in cochlea w/ addition ofkinocilium Basal firing of vestibular nerve occurs in absence of any

stimulus allowing bidirectional regulation

Semicircular Canals Measures angular acceleration through pressure change

exerted on cupula by endolymph in canal

Endolymph lags behind initial movement and thus exerts aforce in opposite direction of head rotation

Vestibulo-ocular reflex - head moves to one side and eyes

move to other Utricle & Saccule

Monitor static head position and linear acceleration

Utricle - horizontal - fire when supine

Saccule - vertical - fire when upright


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Vestibular System

Vestibulospinal - balance & posture Pathology - ataxia

Vestibulocerebellar - reflexes & balance

Vestibulo-ocular - eye movements Pathology - abnormal nystagmus

Vestibulo-cortical - conscious awareness ofposition

Pathology - dizziness/vertigo Vestibulo-autonomic - correlating visual and

vestibular information Pathology - motion sickness


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Spinal Reflexes Stretch Reflex

Sensor = muscle spindle Stretch activates Ia fibers

Ratio of intrafusal to extrafusal fiber determines how fine movementcan be (lower ratio - finer movement)

Golgi Tendon Organ

Senses tension

Ib fibers synapse on inhibitory internerurons

Synaptic delay depends on # synapse in reflex arch

Muscle Spindle

Ia - annulo-spiral endings - respond to rapid

II - flower spray endings - most active when stretched to limit -

proprioceptive info

- efferent mn innervating intrafusal mn in spindle Reciprocal Inhibition

Ia afferents innervate both synergistic and antagonistic muscle

GTO excites inhibitory interneuron which relaxes antagonist muscle

Renshaw cell - gives feedback inhibition on agonist and activationof anta onist when amn is overactive


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Basal Ganglia Disturbances Parkinsonism

Degradation of dopaminergic neurons in substantia nigra Resting tremor, akinesia, bradykinesia, cogwheel rigidity

Huntingtons Chorea Loss of GABA due to med. Spiny neurons (caudate atrophy) Inhibition of indirect loop

Chorea, dementia, deceased tone

Ballism Damage to subthalamic nucleus - inhibition of indirect loop

Flailing movements Athetosis

Damage to GP and Putamen

Wormlike, writhing movements, dystonia (posture issues)

Doesnt go away with sleep Tardive Dyskinesia

Iatrogenic side effect of antipsychotic drugs (thorazine)

Involuntary mouth movements due to supersensitivity of DAreceptors (buccolingual dyskinesia)


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Cerebellum

Neurons - all inhibitory (GABA) except Granule Cells(glutamate) in parallel fibers that synapse of purkinjecells

3 regions of cerebellum

Cerebrocerebellum

dentate nucleus Planning & initiation

Spinocerebellum (vermis & intermediate region) Vermis - fastigial nuclei - medial muscle control

Intermediate - interposed nuclei - lateral muscle control

Vestibulocerebellum (flocculonodular lobe) Vestibular nuclei

Vestibulospinal - posture

Occulomotor - head and eye movements


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Cerebellar Lesions

Lesions - damage is always same side!

Cerebellar Damage

Intention Tremor

Ataxia

Delayed Initiation

Dysmetria (inaccuracy in range & direction)


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Decoricate vs. Decerebrate Rigidity

Decorticate: CNS Damage above level

of Red Nucleus

Rubrospinal Tract active- activates armflexors with response to pain or head turn

in contralateral direction

Decerebrate: CNS Damage at or belowlevel of Red Nucleus

Everything extended except fingers.


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Reticular Formation

Serotonin Raphe Nuclei - descending pain & sleep/wake

Dopamine SN - nigrostriatal path (direct loop)

VTA - reward pathway Norepi

Locus Coeruleus - arousal & selective attention Silent during REM

ACh Pedunclelopontine & LDT - sleep/wake

Active during REM

Basal Forebrain - memory Degenerates in Alzheimers


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Sleep-Wake Cycle

REM Sawtooth waves, mixed frequency EEG

Dreaming, Paralysis

NREM Stage 1 Low voltage, mixed freq

Stage 2 Sleep spindles, K complexes Stage 3 Delta waves

Stage 4 More Delta waves

Reticular Nucleus - inhibitory to all thalamic nuclei Wakefulness - reticular nucleus is inhibited by cholinergic

neurons, locus coerulus & raphe NREM - reticular formation dominant

REM - cholinergic neurons only inhibit RN


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Visual System

Light changes 11-cis retinal to: All-trans retinal

This activates: Transducin

This activates

Phosphodiesterase

This changes: cGMP to GMP

This causes:

Cation channels to close - hyperpolarization Channels open to Na+ and Ca+2

Visual sensation - cessation of NT release(photoreceptors most active in dark)

Retinal pigment epi - restores 11-cis retinal

Documents

Physio - Neuro - Review - Stacey Trent - 2005