Neurophysiology

Cranial nerve reflex testing

Associations with brain regions 1) Prosencephalon: CN I and CN II 2) Midbrain: CN III and CN IV 3) Pons: CN V 4) Medulla: CN VI-XII All cranial nerves enter/exit their respective brain region IPSILATERALLY Prosencephalon processes sensory** information from CONTRALATERAL cranial nerves*** - Example: visual information from right eye processed by left cerebrum General approach to interpreting CN testing abnormalities 1) If a single CN is affected, no other exam abnormalities, prioritize localizing to the CN 2) If multiple CN affected, + other exam abnormalities, prioritize central lesion affecting region(s) of brain associated with affected CNs

SSA: Hearing

Receptor: hair cells in spiral organ within cochlear duct SSA fibers comprise cochlear portion of CN VIII - CN VIII terminates on cell bodies in dorsal and ventral cochlear nuclei in lateral medulla Extensive pathway to ultimately reach auditory cortex

SSA: Vision

SSA fibers carried from retina in CN II (optic nerve) At chiasm, most* fibers cross Travel through contralateral optic tract Reach lateral geniculate nucleus Project from LGN to occipital cortex via optic radiation

SVA: Olfaction

SVA fibers are bipolar neurons in nasal mucosa olfactory epithelium - Cilia project from these olfactory cells and lie in olfactory secretions - Unmyelinated axons travel through cribriform plate to olfactory bulb - Olfactory cells synapse with brush and mitral cells Brush/mitral cell axons project caudally on olfactory peduncle, then through medial/lateral olfactory tracts Lateral olfactory tract terminates in olfactory cortex covering piriform lobe The ONLY sensory system that lacks a thalamic nucleus for projection to the cerebral cortex!

The "Specials"

Special sensory afferent (SSA) - vision, hearing Special visceral afferent (SVA) - taste, smell Special proprioception (SP) - Body/head position, Balance - Eyes, neck, trunk, limbs relative to head position

GVE LMN sympathetic enteric control

Spinal cord segments: - T5-L1 Ganglia: 1) Celiac ganglion 2) Cranial and 3) Caudal mesenteric ganglia Neurotransmitter: - Norepinephrine Distribution: - ALL of GI tract Effect: 1) Inhibition of peristalsis and secretion 2) Increase sphincter tone

Mesencephalon

Structures: - Tectum: rostral and caudal colliculi - Cerebral peduncles: reticular formation, substantia nigra, crus cerebri General functions: 1) Ascending reticular activating system 2) Auditor and visual processing 3) Conduit between cerebrum and caudal structures CN association: CN III and CN IV

GVE LMN parasympathetic** enteric control

**Parasympathetic stim** - Increase GI tract activity - Promote peristalsis - Relax sphincters - Preganglionic neurons: 1) Vagus nerve (from medulla): esophagus, stomach, pancreas, intestines 2) Pelvic nerve (from S1-S3): intestines to anus - Ganglia: Myenteric + submucosal plexuses Parasympathetic supply to the gut is divided into cranial and sacral divisions - Except for a few parasympathetic fibers to the mouth and the pharyngeal regions of the alimentary tract, the cranial parasympathetic nerve fibers are almost entire in the vagus nerves*** - The vagus nerves provide extensive innervation to the esophagus, stomach, pancreas and somewhat less to the intestines down through the first half of the large intestine. - The sacral parasympathetics originate in the first, second, and third segments of the spinal cord and pass through the pelvic nerves** to the distal half of the large intestine to the anus. - The postganglionic neurons of the gastrointestinal parasympathetic system are located mainly in the myenteric and submucosal plexuses. Stimulation of these parasympathetic nerves causes general increase in activity of the entire enteric nervous system

Which of following points are correct about reflex dyssynergia (detrusor urethral dyssynergy) - which drugs can it be treated with?

- Associated with aggression = YES - Goldens predisposed = maybe? - More common in females = NO, MALES - one of the most common causes is spinal cord injury = YES TX 1) Phenoxybenazamine = YES, alpha blocker to internal sphincter 2) Diazepam = YES, external sphincter skeletal muscle relaxation 3) PPA = NO, this is alpha agonist for urinary incotinence 4) Bethanecole - would not recommend b/c only causes bladder to contract but will cause pain if cannot release sphincter 5) Prazosin = YES, alpha blocker (can also use tamulsin) 6) Oxybutynin = NO, muscarinic blocker/antagonist so only affects PNS on bladder contraction

Connecting brain to LMNs: Upper motor neurons

- Functions 1) Initiates voluntary movement 2) Maintains muscle tone for support of body against gravity (neuromuscular spindles) 3) Posture regulation 4) Synapse with interneurons/directly onto GSE LMNs In general, these UMNs are inhibitory to the LMNs - Pathways 1) pyramidal - travel through pyramids on ventral aspect of medulla 2) extrapyramidal (do not travel through pyramids)

SNS innervation to the bladder:

- Hypogastric nerve from L1-L4 lumbar spinal cord (cats = L2-L5): Bladder filling - Preganglionic fiber = nicotinic cholinergic in CAUDAL MESENTERIC GANGLION - Postganglionic fibers: 2 types A) Alpha adrenergic to internal urethral sphincter to maintain sphincter tone during filling B) Beta adrenergic to the detrustor muscle to inhibit contraction

Check the following drugs that can be used to produce bladder contraction

1) Bethanecol = YES cholinergic agonist --> detrusor contraction via M3 receptors 2) Oxybutinin = NO, antispasmotic agent for bladder 3) Cisapride = YES, causes release of ACh 4) Metoclopramide = theoretically YES - central dopamine antagonist but also peripheral direct stimulator of smooth muscle 5) Phenoxygenzamine = Alpha antagonist, relaxes internal urethra but no alpha on bladder contraction

Four important GVE LMN components

1) Control of the pupils 2) Control of micturition and defecation 3) Control of the enteric system 4) Control of the cardiorespiratory system

GVE LMN correlates: Cardiovascular innervation

1) Sympathetic: - Via sympathetic chains - Increases heart rate and contraction - Distributed to ALL parts of heart - Norepinephrine increases sodium and calcium ion permeability Sodium: Hypopolarization Calcium: Increased contractile strength 2) Parasympathetic - Via vagus nerve - Decreases heart rate and contraction - Distributed to SA and AV nodes** - Acetylcholine increases potassium permeability Hyperpolarization: A) Decreased SA node rate B) Decrease excitability of AV junctional fibers Parasympathetic plays very little role in circulation*** 3) Cardiac/vasomotor centers in medulla/pons - To vagus nerve and sympathetic fibers - Vasoconstrictor area: excitatory to sympathetic - Vasodilator area: inhibitory to sympathetic Vessels: 1) Sympathetic: Alpha 1 vasoconstriction 2) Parasympathetic: Some vasodilation Baroreceptor reflex - Baroreceptors: stretch receptors Located in internal carotid arteries and aortic arch When stretched by high blood pressure: Inhibit vasoconstrictor center: inhibit sympathetic impulses Stimulate vagal parasympathetic center - Result: Decrease in arterial pressure Cushing reflex: CPP=MAP-ICP For brain perfusion, arterial BP must be greater than intracranial pressure Hypothalamus activates vasoconstrictor center - Peripheral vasoconstriction - Increase in cardiac output - Increased arterial pressure stimulates baroreceptors - Leads to baroreceptor reflex - Reflex bradycardia

Organizational approach

1. General somatic -GSE -GSA 2. General proprioception 3. General visceral -GVE -GVA 4. "The Specials"

GVE/GVA correlates: GI tract reflexes

3 main pathways/ categories: 1) Entirely within enteric system - Peristalsis, mixing contractions, local inhibitory effects 2) From gut to sympathetic ganglia (These reflexes transmit signals long distances to other areas of the gastrointestinal tract) A) Gastrocolic reflex - Signals from stomach to cause colon evacuation B) Enterogastric reflexes - Signals from intestines to inhibit stomach motility and secretions C) Colonoileal reflex - Signals from colon to inhibit ileal emptying 3) From gut to spinal cord or brain A) Gastric motor and secretory function B) Pain reflexes - GI tract inhibition C) Defecation reflexes

The pudendal nerve:

A) Mediates its effect through norepi at nictonic receptors B) Mediates effect through acetylcholine as muscarinic receptors C) Originates from S1-S3 spinal cord segments ventral horn motor neurons D) Is affected in dysautonomia C is correct - mediates effects via ACH at the NMJ: nicotinic receptors** (N1) - would not be affected in dysautonomia because it is somatic

The PS innervation of the bladder - which is correct?

A) Derives from L1-5 spinal cord segments B) Produces contraction of the external urethral sphincter C) Commonly affected with tail pull injuries D) Produces effect through acetylcholine and the M1 muscarinic receptor C is correct, rest are wrong because: - derived from S1-S3 (remember PNS is CRANIOSACRAL) - Contraction of external urethral sphincter is SOMATIC by pudendal b/c skeletal - bladder has M3* receptors (M1 = CNS, M2 = Heart, M3 = smooth muscle which is bladder, glands)

Which is correct about sensory information related to bladder filling?

A) Is conveyed from stretch receptors in bladder wall via pelvic nerve B) Prevents bladder contraction via hypogastric nerve C) Can be blocked using PPA (phenylpropanolamine D) Is altered in botulism A is correct - sensory information that is not painful travels via PNS** - when reaching appropriate stretch, it would inhibit hypogastric nerve to allow for contraction via PNS - botulism is a neuromuscular disease = nicotinic cholinergic

How do the neuronal cell body (soma) and axon differ?

A) Soma has more voltage gated sodium channels than axon - FALSE - Soma has few voltage gate Na+ channels** B) Internal electrical resistance of soma is lower than axon - TRUE - Cell body relies much more on electrotonic spread of message just like cable conduction = low electrical resistance in soma** - Allows it to conduction messengers further in the cell body - bigger = less resistance C) Resting potential of soma is more negative/polarized than axon - FALSE - More positive; higher RP at -65mV** D) Temporal and spatial summation is important in axon, not soma - Axon is all or nothing, doesn't care - Soma takes all these bits of messages coming in, spreading them around and then summating them at the axon papilla Soma has very different function than axon - neuron cell body has to integrates all the information from neuro system - inhibitory vs excitatory - very copmlex info coming into soma, output is simple: AP triggered or not

functional classification

Afferents: sensory systems - Somatic - Visceral - Proprioceptive Efferents: motor systems - Somatic - Visceral

Reflex arcs

All reflex arcs have: 1) Peripheral sensory component (GSA) 2) Central component In spinal cord for spinal reflexes In brain region for cranial nerve reflexes 3) Peripheral motor component (GSE) A lesion anywhere WITHIN the reflex arc will lead to decreased** reflexes A spinal cord lesion CRANIAL to a reflex arc can lead to increased** reflexes Some cranial nerve tests evaluate responses, not reflexes Response = learned Cranial nerve testing evaluates: 1) Cranial nerves 2) Specific brain regions

GVE LMN: Micturition

Anatomy of local reflex arc 1) Muscle anatomy: A) Detrusor muscle: smooth muscle syncytium B) Internal urethral sphincter: smooth muscle C) External urethral sphincter: skeletal muscle 2) GVA A) Bladder distension: pelvic nerve (sensory fibers from bladder to spinal cord) B) Pain: pelvic and hypogastric C) Urethral urine flow: pudendal *3 nerves sending sensory to brain = pelvic, hypogastric, pudendal 3) GVE A) Sympathetic * Hypogastric nerve, L1-L4 (via caudal mesenteric ganglion) sns to: - detrusor muscle (via beta = RELAXATION to allow filling) - Internal urethral sphincter (via alpha = constrict sphincter) - parasympathetic ganglion / LMNs to inhibit PNS fibers going to detrusor mm to further inhibt contraction B) Parasympathetic * Pelvic nerve, S1-S3 - To detrusor muscle --> release ACH, stim contraction ==> major excitatory mechanism for urination 4) GSE A) Pudendal nerve, S1-S3 - LMN To external urethral sphincter Micturition supraspinal reflex - GVA: - First order sensory neurons synapse with second order neurons (spinal cord) --> Second order neurons ascend spinal cord to micturition center in pontine reticular formation - Information about bladder fullness: Through thalamus to cerebral cortex Fibers from motor cortex to pontine micturition center * Conscious urine storing and voiding - GVE Upper motor neurons: - Descend from pons via pontine reticulospinal tract - Synapse with lower motor neurons in L1-L4 (sympathetic) and S1-S3 (parasympathetic and somatic) Micturition: (stim PNS, inhibit SNS/somatic efferents) 1) When the bladder is full, stretch receptors in the bladder wall signal the brainstem micturition center in the pontine reticular formation 2) Parasympathetic efferents in the pelvic nerve stimulate contraction of the detrusor muscle by release of acetylcholine ** This is the major excitatory mechanism that results in the flow of urine 3) Sympathetic efferents in the hypogastric nerve are INHIBITED via descending pontine reticulospinal input. - The inhibition of adrenergic fibers allows the internal urethral sphincter to relax and the inhibition of beta adrenergic fibers discontinues active relaxation of the detrusor muscle 4) Somatic efferents in the pudendal nerve are inhibited by descending pontine reticulospinal input. This allows the external urethra sphincter to relax.

GVE LMN correlates: UMN Bladder

Caused by disorder cranial to S1-S3 1) Increased sphincter resistance - Uninhibited activity of external urethral sphincter 2) Alpha receptors uninhibited - Increased activity of internal urethral sphincter Bladder is tense, difficult to express Intermittent overflow incontinence Common in patients with T3-L3 myelopathy Treatment: - Skeletal muscle relaxants: 1) Diazepam** 2) Dantrolene - Alpha adrenergic antagonists** 3) Prazosin** 4) Phenoxybenzamine**

Telencephalon

Cerebrum Surface structures: - Divided into two cerebral hemispheres - Outward folds = gyri - Inward folds = sulci Internal structures: - Internal capsule - Basal nuclei Functions: 1) Gait generation 2) Conscious awareness 3) CN associations: CN I

GVE LMN correlates: enteric system control

Components: - Sensory - Enteric nervous system - Parasympathetic LMNs - Sympathetic LMNs - GI tract reflexes Nerve endings in GI epithelium and gut wall GSA fibers to: - Enteric plexuses + Sympathetic prevertebral ganglia --> Brainstem via vagus nerve *** --> Pelvic nerves to S1-S3 Elicit: - Local reflexes within gut wall itself - Reflexes involving paravertebral ganglia, brainstem, S1-S3 GVE/GVA Two plexuses: 1) Myenteric plexus (muscle) - Between longitudinal and circular muscle - Controls peristalsis 2) Submucosal plexus - In submucosa - Controls secretion and local blood flow Neurotransmitters: A) Acetylcholine: excitatory B) Norepinephrine: inhibitory The enteric nervous system can function on its own but stimulation by the sympathetic and parasympathetic systems can greatly enhance or inhibit gastrointestinal functions

GVE LMN: Control of pupils - PNS

Constant balance between environmental light (parasympathetic) and emotional status (sympathetic) PNS: 1) Preganglionic cell body location: - Parasympathetic nucleus of cranial nerve 3 - Rostral midbrain 2) Cranial nerve carrying preganglionic axons: - CN III (oculomotor) 3) Ganglion: - Ciliary ganglion 4) Effector organ: - Postganglionic axons to ciliary body 5) Effect: - Pupillary constriction What would you expect with dysfunction of parasympathetic portion of CN 3? CN 3 also innervates the extraocular muscles. Therefore, the constellation of neuro exam abnormalities that you would expect to see with dysfuction of CN 3 include: 1) Absent PLR in the affected eye both direct and indirect 2) Mydriasis 3) External and internal ophthalmoplegia 4) Ptosis 5) Ventrolateral strabismus

Brain region summary

Developmental divisions: 1) Telencephalon: Cerebrum 2) Diencephalon: Thalamus + friends 3) Mesencephalon: Midbrain 4) Metencephalon: Pons + Cerebellum 5) Myelencephalon: Medulla oblongata

What is the pituitary derived from? hormones produced where?

Ectoderm - anterior = oral ectoderm folded up from hard palate (Rathke's pouch) - posterior = neural ectoderm, grows downward Anterior - releasing hormones released at median eminence from hypothalamus, taken up into portal vessels to adenohypophysis to release following: - TSH (from thyrotropes) * glycoprotein - GH (somatotropes) *peptide - LSH, FSH (gonadotropes) * glycoproteins - ACTH (corticotropes) *polypeptide - Prolactin (lactotropes) *polypeptide Posterior - peptide hormones made in neurons / transported down to posterior, signals affecting neurons directly = very important - ADH - made in supra-optic nucleus of hyopthalamus - Oxytocin - made in paraventricular nucleus

Extrapyramidal UMNs

Extrapyramidal system - Cell bodies in nuclei in all brain divisions 1) Telencephalon: cerebral cortex, basal nuclei 2) Diencephalon: subthalamus 3) Mesencephalon: substantia nigra, red nucleus 4) Metencephalon: pontine reticular formation 5) Myelencephalon: medullary reticular formation, olivary nucleus - Axons do not travel through pyramids - Recruit spinal reflexes for initiation of voluntary movement - Prominent tracts: rubrospinal, pontine reticulospinal, medullary reticulospinal

SP: Central** Vestibular system

Four vestibular nuclei in rostral medulla - Receive information from ipsilateral CN VIII and ipsilateral flocculonodular lobe - Ipsilateral projections to: 1) Spinal cord 2) Medial longitudinal fasciculus 3) Reticular formation, vomiting center 4) Flocculonodular lobe of cerebellum 5) Somatoensory cortex* Remember that fibers that travel rostrally through brain CROSS at the junction between the midbrain and thalamus. So, information from a patient's right vestibular system is processed by the left cerebral somatosensory cortex Flocculonodular lobe of the cerebellum - Crosstalk with ipsilateral vestibular nuclei - Fibers between vestibular nuclei and FN lobe use caudal cerebellar peduncle

Recap Neuro Organization

GSE LMNs - In spinal nerves of C6-T2 and L4-caudal - In cranial nerves III, IV, V, VI, VII, IX, X, XI, and XII GSA pathways Reflex arcs involving GSE LMNs and GSAs (both spinal and cranial nerves) GP pathways GVE LMNs and GVAs SSAs, SVAs, SP UMNs Brief characterization of brain regions

PNS vs. SNS - GVE

Hypothalamus - Rostral portion subserves PARASYMPATHETIC** GVE LMNs - Caudal portion subserves SYMPATHETIC** GVE LMNs Additional important distinctions between sympathetic and parasympathetic GVEs: 1) Axon length: - PNS = long PRE**ganglionic, short post** ganglionic. Because PNS more involved in local effects (post can be short) -SNS = short preganglionic, long post ganglionic. Because SNS more involved in diffuse effects (need longer reaching post) 2) Postganglionic neurotransmitter - PNS = postganglionic fiber releases acetylcholine - SNS = postganglionic fiber releases norepinephrine EXCEPTIONS: SNS fibers to sweat glands, piloerector muscles, some blood vessels = sympathetic CHOLINGERIC innervation 3) Ganglia: - PNS Ganglia = found in plexuses that ARE associated with the effector organs, so postganglionic axons don't have far to travel - SNS ganglia = distributed throughout the body in three main types: 1) Paravertebral: the sympathetic chain ganglia 2) Prevertebral: found at the cervicothoracic junction 3) Terminal: end of the line. No more ganglia for the preganglionic axons to reach after these ganglia

Autonomic Nervous System: Higher Centers of CNS (GVE)

Hypothalamus: primary integrating center*** - Rostral portion subserves PARASYMPATHETIC** GVE LMNs - Caudal portion subserves SYMPATHETIC** GVE LMNs Projections TO hypothalamus: 1) From cerebrum 2) From thalamic nuclei 3) From ascending general visceral afferent (GVA) pathways Projections FROM hypothalamus: 1) To metabolic centers in reticular formation*** in midbrain, pons, medulla - Control activity of visceral smooth muscle, glands, cardiac muscle via GVE LMNs***

GVE LMN correlates: LMN bladder

Lesion in S1-S3 region 1) Sphincters relaxed 2) Bladder atonic Bladder easy to express Continuous urine overflow Large amount of residual urine Treatment: - Parasympathomimetics: Increase detrusor tone 1) Bethanecol****

Functional classification: general visceral efferent (GVE) system

Look at slide 15 session 14 ppt IMAGE for SNS vs. PNS Functions 1) LMNs of the autonomic nervous system 2) Innervate smooth muscle of blood vessels, visceral structures, glands, cardiac muscle Locations - GVE LMNs are TWO NEURON systems 1. First neuron cell body is in CNS** 2. Second neuron cell body is in a ganglion** Parasympathetic - Preganglionic neuron in brainstem nuclei of CN III, VII, IX, and X + spinal cord segments S1-S3 Sympathetic - Preganglionic neuron in spinal cord segments T1-L4/5

Functional classification: general somatic efferent

Lower motor neurons (LMNs), innervate skeletal (striated) muscle** 1) Select spinal nerve GSE LMN Functions - Final motor innervation of muscles - Motor component of reflexes Locations: - Cell bodies located in specific spinal cord regions Thoracic limbs: C6-T2 Pelvic limbs + caudal: L4-S3 - Axons travel as named nerves LOOK AT IMAGES OF NAMED PERIPHERAL NERVES (e.g. radial, axial - unsure if need to know exact order) 2) Cranial nerve GSE LMNs: - III, IV, V, VI, VII, IX, X, XI, XII Functions - Final motor innervation of voluntary striated skeletal muscle derived from occipital somites - Motor component of cranial nerve reflexes Locations - Cell bodies located in specific brain regions - Axons travel as named nerves *** chart in session 14 neurophysiology

Horner syndrome (sympathetic chain lesion)

Most common cause of Horner syndrome in dogs and cats is otitis media/interna, but it can also happen due to venipuncture if you are too close to the vagosympathetic trunk when drawing from the jugular vein. 1) Miosis (PNS from III acts unopposed on iris sphincter) 2) enophthalmos (periorbital smooth muscle relax from loss of SNS) 3) third eyelid elevation (Passive in dogs secondary to enophthalmos, active in cats from loss of SNS smooth muscle contraction in third eyelid) 4) ptosis (drooping upper eyelid) 3-neuron pathway SNS innervation to eye - 1st order (central) from hypothalamus --> down spinal cord to 2nd order neuron (preganglionic) from T1-T4 --> back through thorx/cervical region to cranial cervical ganglion --> third order / postganglionic goes to orbit topical 1% phenylephrine allows for ID / LOCALIZATION of post-ganglion Horner's (gold standard is 5-10% cocaine for confirming horner's) - lesion affecting any part of oculosympathetic pathway will prevent normal release NE - phenylephrine 1% = direct sympathomimetic --> dilates pupil if POST ganglionic lesion (aka lack of noepi release); no effect on preganglionic/central lesions - due to denervation hypersensitivity following absence of endogenous norepinephrine in the affected eye (must use DILUTE solution so only very sensitive eye will respond) When the lesion is preganglionic, however, small quantities of norepinephrine continue to be released by the still-functional postganglionic neuron - 3rd order Horner's syndrome lesion along any part of pathway = same clinical horners signs - central brainstem lesion will also show other signs such as altered mentation, CP deficits, other CN deficits, ataxia (propioceptve >> vestibular) Etiologies: 1) Postganglionic: neoplasia, paraganglioma, idiopathic, iatrogenic (e.g. TECA postop), Infectious (otitis media/interna) 2) Preganglionic: Idiopathic, iatrogenic (epidural, brachial plexus block, thoracic sx), traumatic, neoplastic (mediastinal lymphoma, PNST of vagys nerve), infectious (tick paralysis - Ixodes) 3) Central: traumatic, infectious (neospora), fibrocartilagneous embolisms unspecified = diabetic polyneuropathy

Steps in Neurotransmission

Neurotransmitter of the somatic NS: acetylcholine*** Steps of neurotransmission: 1) Action potential reaches terminal 2) Voltage gated Ca channels open 3) Synaptic vesicles fuse with terminal membrane 4) Acetylcholine released into synaptic cleft 5) Acetylcholine binds to receptors 6) Ligand-gated Na/K channels open --> end plate potential 7) Acetylcholinesterase degrades acetylcholine

Parasympathetic NS questions

Preganglionic PSN neurons originate from which of the following nuclei - PS of nucleus CN III - Yes (PNS = constriction) * Ganglia = ciliary --> ciliary + irish sphincter mm - PS of nucleus CN IV - PS of nucleus CN VI - PS of nucleus CN VII - Yes (PNS = lacrimation/salivation) * Ganglia = Pterygopalatine ---> lacrimal gland * Ganglion = Mandibular ---> submandibular salivary gland - PS of nucleus CN IX - Yes (PNS = carotid sinus nerve / parotid glands) * Ganglia = OTIC --> parotid + zygomatic salivary gland - PS of nucleus CN X - Yes (vagus nerve) - PS of nucleus CN XII - Intermediolateral nucleus in the lateral horn of cervical spinal cord - NO just SNS - Intermediolateral nucleus in the lateral horn of thoracolumbar spinal cord - NO just SNS - Sacral PS nucleus of the intermediate zone of the sacral spinal cord - Yes WILL MOST LIKELY BE ASKED ABOUT NERVES AND THEIR FINAL TARGET SNS = Starts hypothalamus exits thoracolumbar spinal nerves PNS = Comes out of cranial nerves and goes all the way spinal nerves and goes out sacral nerves - no exit points before the sacral spinal cord

GVE LMN correlates: the adrenal glands

Preganglionic cell body location: - T5-T9 Preganglionic axons location: - Splanchnic nerve** Sympathetic ganglion: - Adrenal medulla Modified postganglionic neuronal cells in medulla Neurotransmitter released: 1) Epinephrine 80% 2) Norepinephrine 20% Effect: - Vasoconstriction (mild) - Increased heart rate and contractility Epinephrine** acts more strongly on beta receptors in heart than norepinephrine - Pupillary dilation

GVE Sympathetic

Preganglionic cell body locations: - Lateral/ventral horn of spinal cord segments T1-L4 Preganglionic axon locations: - Leave spinal cord via ventral nerve root - Travel via ramus communicans to sympathetic trunk Trunk dotted with sympathetic trunk ganglia at each spinal cord segment Other ganglia outside the trunk Synapse within one of these ganglia 5 fates of postganglionic axons: 1) Leave ganglion, return to spinal nerve at same level - very small type C fibers that then travel with skeletal nerves to control regional blood vessels, sweat glands, and piloerector muscles. 2) Run rostral or caudal in sympathetic trunk 3) Go directly to visceral structure or join ventral branches to brachial plexus 4) Leave cranial cervical ganglion for distribution to head 5) Leave autonomic plexus ganglia, travel along arteries to abdominal viscera Ganglia: 1) Cranial cervical ganglion - Head and neck 2) Middle cervical ganglion - Thorax 3) Cervicothoracic ganglion - Thorax 4) Celiac ganglion - Abdomen 5) Cranial mesenteric ganglion - Abdomen 6) Caudal mesenteric ganglion - Abdomen and pelvic region Neurotransmitter: Norepi Receptors: Alpha adrenergic, beta adrenergic

GVE parasympathetic

Preganglionic cell body locations: 1) Nuclei in midbrain and medulla 2) Nuclei in lateral horn of sacral spinal cord segments Preganglionic axon locations : 1) CN: III, VII, IX, X (oculomotor, facial, glossopharyngeal, and vagus) - 75% of all PSN fibers are in the vagus nerves: - Vagus = PNS innervation to the heart, lungs, esophagus, stomach, entire small intestine, proximal half of the colon, liver, gallbladder, pancreas, kidneys and upper portions of the ureters. 2) Pelvic nerves S1-S3 - descending colon, rectum, urinary bladder and lower portions of the ureters as well as genitalia. Neurotransmitter: Acetylcholine Receptors: Muscarinic acetylcholine receptors

SP: Vestibular system

Processes information about: - Gravity - Body rotation - Acceleration Maintains: - Body/head position - Balance - Eyes, neck, trunk, limbs relative to head position

Pyramidal UMNs

Pyramidal system - Cell bodies in motor area of cerebral cortex - Axons travel through the pyramids on ventral surface of medulla** - 75% of axons cross in the pyramids to continue contralaterally - Remaining 25% cross close to synapse with GSE LMNs Comprise lateral corticospinal, ventral corticospinal, and corticonuclear tracts Terminate on GSE LMNs Disturbances in dogs/cats generally does not lead to gait dysfunction but will lead to postural reaction deficits**

Impulse conduction

Question 4: which of the following statements about impulse conduction is correct A) Local anesthetics block conduction by blocking voltage gate d potassium channels - FALSE - Block SODIUM channels B) Myelin decreases membrane capacitance and increase membrane resistance - TRUE - If you have a membrane with high resistance, none of the local spread of current will be spent trying to charge the nerve/membrane capacity, decreases need to charge everything - Simple cable conduction / myelinated conductions - Very fast, but will die out - Node of Ranvier between the myelin where the action potential can renew itself (little spaces between myelin) - Saltatory conduction C) As axon diameter increases, speed of conduction decreases - FALSE - Bigger axon = faster conduction; by the square D) Nerve conduction is unidirectional - FALSE - Messages can go in both directions - In biological state - message starts at one end of the nerve and generally does go in one direction - But truth is, nerve conduction can go in both directions

Synaptic transmission / neurotransmitters

Question 5: Synaptic transmission has the following properties: check all those that are correct A) Intracellular flow of Ca++ is vital for neurotransmitter release - TRUE B) Excitation of the post-synaptic membrane can be achieved through influx of sodium or influx of potassium - FALSE - Efflux potassium C) Inhibition of the post-synaptic membrane can be achieved through efflux of chloride - FALSE - Influx of chloride D) Synaptic transmission is energy dependent - TRUE E) Receptors may include ion channels or second messenger activators - TRUE Question 6: which of the following statements about neurotransmitters is correct? A) Thyrotropin-relasing hormones (TRH) a slow acting neuropeptide transmitter - TRUE B) Acetylcholine interacts with alpha adrenergic receptors - FALSE - Muscarinic C) Gaba, glycine, glutamate are inhibitory neurotransmitters - FALSE - VERY IMPORTANT EXCITATORY D) Dopamine is a critical excitatory neurotransmitter - FALSE - INHIBITORY** (think add causes inhibition gut movement) Classes of neurotransmitter 1) Small molecules - rapidly acting - synthesized at pre-synaptic terminal - typically open an ion channel 2) Neuropeptides - synthesized in soma (transported down to nerve ending) - Slow acting - Act via second messenger Question 8: neuromuscular transmission relies upon A) Norepinephrine - FALSE - Neuromuscular transmission is CHOLINERGIC*** ACH B) SNARE proteins - TRUE - Allow vesicles to dock and release, CRTICAL C) Calcium efflux - FALSE - Calcium comes INSIDE, not outside D) Inhibitory post-synaptic receptors - FALSE - No inhibitory post-synaptic receptors Question 9: which of the following statements is correct? A) Neostigmine is an acetylcholine antagonist - FALSE - Cholinesterase inihibtor B) Edrophonium prevents choline uptake by presynaptic membrane - reversible acetylcholineserase inhibitor C) Curare is an antagonist at nicotinic cholinergic receptor D) Pyridostigmine adminstered IV - ORAL: Mestinon tablets Preglanglionic - which is correct? A) SNS Preganglionic NT/receptor = norepi/alpha adrenergic - FALSE - that combo would be POST ganglionic B) PS preganglionic NT/receptor = acetylcholine/muscarinic - FALSE - muscarinic is POST ganglionic C) PS an S preganglionic NT/receptor = glutamate/NMDA - FALSE - glutamate and NMDA does NOT come into the AUTONOMIC nervous system, glutamate most abundant excitatory in the CENTRAL nervous system D) PS and S preganglionic NT/receptor = Acetylcholinee/nicotinic - CORRECT - N1 = neuromuscular junction - N2 = preganglionic Match correct cholinergic receptor to target + effect - M2 = HEART --> PNS slowing HR, detrusor - M3 = SMOOTH MUSCLE = bronchioles, detrusor - M5 = SWEAT / MEROCRINE GLANDS What is the major difference between cholinergic nicotinic and muscarinic receptor? - niconic = iontropic (opens ION CHANNELS) - muscarInic = G PROTEIN LINKED Adrenergic receptors 1) Are these ion channel or second messenger receptors = 2ND MESSENGER 2) Where do you find alpha receptors, what do they do - vasculature, vasoconstriction 3) Where do you find beta receptors + subtypes - B1 = HEART - positive inotrope, chronotropy - B2 = LUNGS - bronchodilation

Functional classification: general visceral afferent (GVA)

Receptors - Located throughout viscera - respond to distension, pressure, stretch, chemical changes, pain General visceral afferents - Travel to CNS mainly via 3 cranial nerves: 1) Facial nerve: From salivary and lacrimal glands 2) Glossopharyngeal nerve: Pharyngeal mucosa, caudal 1/3 of tongue and carotid sinus 3) Vagus nerve: Larynx, trachea, esophagus, thoracic and abdominal viscera Vagus is 80% GVA fibers Cell body location: distal vagal ganglion - Share a common nucleus in medulla**: Solitary nucleus**

SP: Peripheral** Vestibular system

Receptors of the vestibular system: - Utricle and saccule: detect linear acceleration, gravity - Semicircular ducts: detect head rotation Information from these receptors carried by CN VIII - CN VIII travels from the inner ear to the rostral medulla

GVE Neurotransmitter Receptors

Receptors on effector organs: - Acetylcholine 1) Nicotinic : found on the autonomic ganglia at the synapses between the preganglionic and postganglionic neurons of both the sympathetic and parasympathetic systems 2) Muscarinic : found on all effector cells that are stimulated by the postganglionic cholinergic neurons of either the parasympathetic or sympathetic nervous system - Norepinephrine 1) Alpha 1 and 2 : smooth muscle contraction and one inhibitory function: intestinal relaxation 2) Beta 1 and 2 : mediate relaxation or decrease activity of effector cells; EXCEPTION: Increased heart rate and contractility Norepinephrine excites mainly alpha cells but beta cells to some extent as well Epinephrine excites both receptors equally - Dopamine

SVA: Taste

Receptors: taste buds - SVA fibers synapse with taste buds From rostral 2/3 of tongue: CN VII From caudal 1/3 of tongue: CN IX From caudal pharynx/larynx: CN X - Enter solitary tract** in medulla (same tract for vomiting center) Solitariothalamic tract projects to cerebral cortex

GVE Neurotransmitters

Secretion of neurotransmitters - Varicosities: postganglionic nerve endings generally touch the effector organ or end in adjacent connective tissue. At their ends, they have bulbous enlargements called varicosities. The neurotransmitters are synthesized and stored within the varicosities. Ca++ influx from AP cause vesiocular migration to release neurotransmitters - Mitochondria varicosities also contain large numbers of mitochondria to supply ATP for neurotransmitter synthesis. Acetylcholine metabolism - Acetyl CoA and choline - Choline acetyltransferase - Acetylcholinesterase ACH synthesized from Acetyl CoA and choline, catalyzed by choline acetyl-transferase. Once acetylcholine has been released, it persists in the tissue for a few seconds before being hydrolyzed by acetylcholinesterase. The choline is then resorbed to be used in formation of more acetylcholine. Norepinephrine metabolism - Epinephrine metabolism: Main hormone leased from adrenal medulla Norepi synthesized in the axoplasm of the terminal nerve endings of adrenergic nerve fibers. Synthesis is completed in the vesicles. Phenylalanine is converted to Tyrosine, which is hydroxylated to form Dopa. Dopa is then decarboxylated to form Dopamine. Dopamine is then transported into the vesicles, where it is hydroxylated into norepinephrine or remains in this form if it is in the CNS. In the adrenal medulla, the reaction goes one step further with methylation of norepinephrine to create epinephrine. 80% of the vesicle contents released from the adrenal medulla are epinephrine. After it is secreted, norepinephrine is cleared from the synapse in three ways: 1) reuptake into the adrenergic nerve endings via an active transport process. This accounts for removal of 50-80% of norepinephrine. 2) diffusion away from the nerve endings into the surrounding body fluids and then into the blood 3) destruction of small amounts by tissue enzymes Norepinephrine secreted directly into the tissue remains active for only a few seconds. But norepinephrine and epinephrine secreted into the blood remain active until they diffuse into some tissue. This equates to activity of about 30 seconds. Dopamine metabolism - CNS neurotransmission see norepi above

Functional classification: General somatic afferent (GSA) and general proprioception (GP)

Sensory system general scheme: - Peripheral afferent neuron, dendritic zone modified to be a receptor organ Axon courses toward CNS Cell body is in ganglion - Central relay nucleus and tract that courses to specific thalamic nucleus - Thalamic nucleus relays to specific area of cerebral cortex Functions - GSA: detect temperature, touch, nociception - GP: detect position and movement in muscles and joints GSA specifically: Function Detects temperature, touch, nociception For conscious awareness For reflex arcs Receptors: thermoreceptors, mechanoreceptors, nociceptors Location All spinal nerves** Many cranial nerves (mainly CN V***) Ascending tracts ultimately reach contralateral somesthetic cerebral cortex Nociceptive pathway: - spinothalamic tracts Other pathways: - dorsal column postsynaptic pathway, - spinocervicothalamic pathway, - spinomesencephalic pathway GP specifically Function: Detects position and movement in muscles and joints Two basic pathways: 1) For segmental reflex activity + transmitting proprioceptive information to cerebellum 2) For conscious proprioception

Action potentials

Short answer question: describe the ionic changes occurring in the depolarization - different phases and what is happening to sodium + potassium permeability - Threshold -55mV: rising voltage trigger by chemical or electrical signal reaching enough of threshold, generate all or nothing action potential with a burst of sodium channels open = depolarization - rising voltage also triggers slower closing of Na channels - Sodium levels out as they close, - now voltage gated potassium channels open (open more slowly) and they flood out - All voltage gated and time-sensitive (closure slower than opening) - Repolarization triggers closing of K+ channels - Can "overshoot" with repolarization but eventually will level out back to resting state Absolute refractory = cannot make that axon fire again b/c not yet repolarized Relative refractory period = HYPERPOLARIZED so more of a depolarization to reach threshold to produce action potential Question 3: which of the following facts about an action potential are correct - check all that apply A) Action potential is all or nothing - TRUE B) Action potential cannot be generated during refractory period - FALSE (absolute vs. relative) C) Calcium concentration affects threshold of activation of an action potential with higher concentrations making the threshold more negative - FALSE - Calcium stabilizes the sodium channel, when you do not have ca+ sodium channel becomes more excitable (tetany with hypocalcemia) - Calcium does NOT alter threshold itself - If you have more calcium, the threshold is more POSITIVE D) Action potential propagates through the local spread of current - TRUE

Myelencephalon (medulla oblongata)

Structures 1) Trapezoid body 2) Pyramids 3) Longitudinal fibers Functions 1) Ascending reticular activating system 2) Conduit for GSA, GP, SP, GSE, GVE pathways** CN associations: CN VI-XII**

Diencephalon

Thalamus: cortical projection system - Main sensory integrating system, connecting caudal brainstem and cerebrum - Part of ascending reticular activating system Hypothalamus - Regulation of visceral motor activity** - Refer to endocrine lectures for more details CN associations: CN II

4 Diagnostic Criteria for Dysautonomia

The dysautonomias are a group of diseases with strikingly similar clinical and pathologic signs reported in a number of unrelated species, including horses, dogs, cats, rabbits, and hares. The disease is characterized by the degeneration of neurons in autonomic ganglia and clinical signs of autonomic nervous system dysfunction. The etiology is unknown in all species, and there is no effective treatment. - loss of SNS from neural depletion in ganglia AUTONOMIC signs: - Megaesophagus - Severe ileus / dysphagia - Tachycardia or bradycardia that is not responsive to atropine - Decreased tear production (dry eyes/nose) - urine retention - blood pressure = hypotensive independent of HR - Mydriasis without PLR, elevated 3rd eyelids: - decreased anal reflex Pharmacologic tests: - dilute pilocarpine = quickly constricts pupils due to deinnervation hypersensitivity - improved ability to urinate with admnistration of bethanechol - no change in HR during 60 mins post administration atropine - absence of falre response to intradermal histamine (need to vasodilate to get blood there for response test) Risk factors for canine dysautonomia? - rural (central/south) - Outdoor, young male dogs - Time of year: Feb to April - Diet = consumes wildlife

Spinal Reflex Testing

Thoracic limb reflex: - Withdrawal: C6-T2; all thoracic limb nerves; all flexors Pelvic limb reflexes: - Patellar: L4-L6; FEMORAL nerve, extensor muscles - Withdrawal: L6-S1; SCIATIC nerve, flexors Cutaneous trunci: C8-T1; SENSORY (segmental spinal nerves) + MOTOR (lateral thoracic nerve) Perineal: S1-S3, PUDENDAL nerve Anal sphincter tone: S1-S3, CAUDAL RECTAL n, external anal sphincter

GVE LMN: SNS to the eye

UMNs from hypothalamus via lateral tectotegmentospinal tract** Preganglionic cell body location: - Lateral horn T1-T4 *** remember all SNS of GVE comes from spinal segments T1-L5 Nerve carrying preganglionic axons: - Ventral root --> ramus communicans -->sympathetic trunk --> vagosympathetic trunk --> Ganglion: - Cranial cervical ganglion - Pass through tympanic bulla - Travel with CN V to orbit Effector organ: 1) Orbitalis muscle 2) Ciliary body 3) Pupillary dilator Effect: Pupillary dilation Sympathetic denervation to the head: - Horner syndrome*** - Vasodilation: increases blood flow to the denervated area 1) Palpable hyperthermia 2) Sweating in horses - In all domestic animals beside horses, sweating is decreased on the surface of the body that as been deprived of its sympathetic innervation. Horses with denervation get excessive sweating. Exact mechanism unknown but prevailing hypothesis: Sudden vasodilation increases blood flow carrying circulating norepinephrine, which stimulates excessive sweating 3) Nasal vasodilation leads to nasal congestion - Anhydrosis Dry nasal planum

General points about ANS

Which of the following is true? A) PNS but NOT SNS require 2 neurons from nucleus of origin to target - FALSE - all have 2 neurons (pre inside nucleus of origin and postganglionic) B) Hypothalamus controls the ANS via reticular formation - TRUE - Hypothalamus is the head of the ANS / start of ANS C) Chromaffin cells of adrenal medulla are modified post ganglionic neurons of PNS - FALSE - SYMPATHETIC** D) Junction between post ganglionic neuron and target is via neuromuscular junctions - FALSE - NMJ is between motor neuron & skeletal muscle SPECIFICALLY - For ANS - post ganglionic communicates via a structure called varicosities Which of the following targets are innervated by ONLY SNS: - Detrusor muscle - BOTH PSN (contraction) + SNS (relaxtion) - sweat merocrine glands - only SNS - lacrimal glands - PNS - pancreatic isles - both? - GI sphincters - PNS** - Arrector pili - only SNS - Veins - only SNS - Salivary glands - Pineal glands - only SNS - AVN - both PNS/SNS - Bronchiolar muscle - both Can you draw basic layout of ANS as it leaves CNS + hits target 1) PNS pre-ganglionic ----------->(ach) post ganglionic --> (muscarninc) target 2) SNS pre-ganglionic --> (ach) post-ganglionic ---------> (adrenergic) target Details on SNS** Ganglia - which is correct? A) The middle cervical ganglia are the source of post ganglionic fibers for the heart - CORRECT ** B) All preganglionic SNS fibers synapse in a sympathetic trunk ganglion from which post ganglionic fiber emerges - FALSE - Other areas like adrenal medulla with modified post ganglionic cells - collateral ganglia under the aorta C) Fibers that innervate head / neck from spinal cord segments T1-7 - T1-T5*** - T1-T3 = head; T1-T5 neck D) Splanchnic nerve takes post ganglionic fibers from TL spinal cord segments to abdominal viscera - Pre-ganglionic*** fibers from TL to abdominal viscera Which of following statements is correct? A) Communicating branch contains preganglionic fiber only - FALSE - contains BOTH pre and post B) - Celiac ganglion contains post ganglionic nerve cell bodies targeted to the kidney - celiac = CRANIAL ABODOMINAL / Viscera - THERE IS A RENAL GANGLIA C) Vertebral nerve conveys post ganglionic fibers from cervico-thoracic ganglion to spinal nerves to reach to the arrector pili of neck region - way that the autonomic nerves get back to the spinal nerves and sitrubted up to the skin, hair, etc D) Ansa subclavia is a blood vessel that circles around the subclavian artey - FALSE - Ansa subclavia is a NERVE , splitting of the middle cervical ganglion LOOK AT OLGBY'S DIAGRAM OF SNS GANGLIA in notes - can have a series of three when dealing with the neck/head (cervicothoracic, middle cervical, cranial cervical)

membrane potential

Which of the following statements about membrane potential is correct? A) Sodium-potassium pump pumps 2 sodium ions out for ever 3 potassium ions pumped in - INCORRECT - 3 sodium OUT for every 2 potassium in - Must be sending out more positives than negatives B) Resting membrane potential of -90-mV indicates outside of membrane is negative compared to inside - INCORRECT -90mV = INSIDE negative compared to outside - When an action potential goes down, there is a flood of sodium INSIDE so must be negative inside C) Resting MP results from combo of high intracellular na + high extracellular K - partial membrane permeability and sodium potassium pump - INCORRECT - EXTRACELLULAR NA+, intracellular K+ D) Normal resting nerve fiber, permeability to potassium is 100x greater than to sodium - CORRECT Sodium potassium pump present everywhere - Leak channels much more permeability to POTASSIUM than sodium - slight leak of potassium - If inside was only permeability to potassium = -94, if you now have permeability sodium would be -86mV, adding in the sodium potassium pump creates the -90mV

adrenergic receptors (GVE neurotransmission)

location + action

Metencephalon

pons, cerebellum, fourth ventricle Pons: 1) Ascending reticular activating system 2) Conduit between cerebrum and caudal structures 3) Conduit for cerebellar projections CN association: CN V Cerebellum - The great regulator of movement - Cerebellar afferents: 1) General proprioception 2) Special proprioception (vestibular) 3) SSA (visual and auditory) 4) UMNs - Cerebellar efferents: 1) From cerebellar cortex to vestibular nuclei 2) From cerebellar nuclei to vestibular nuclei, reticular formation, red nucleus, pallidum, ventral lateral nucleus of thalamus

Temporal muscle symmetry

sensory nerve: - motor nerve: CN V result: symmetry. no atrophy

Fixed strabismus

sensory nerve: - motor nerve: CN III, IV, VI result: Normal pupil vector

Lip tone/symmetry

sensory nerve: - motor nerve: CN VII result: symmetry. no drooping

pupillary light reflex

sensory nerve: CN II (optic) motor nerve: CN III (oculomotor) result: pupil constriction

Menace response

sensory nerve: CN II, contralateral cerebral cortex motor nerve: CN VII result: blink

Gag reflex

sensory nerve: CN IX and X motor nerve: CN IX and X result: Cough / repel finger

Palpebral reflex

sensory nerve: CN V motor nerve: CN VII result: blink

Nasal sensation

sensory nerve: CN V, contralateral cerebral cortex motor nerve: - result: response to noxious stimulus

Positional strabismus

sensory nerve: CN VIII motor nerve: - result: Eyes track with head position

Physiologic nystagmus

sensory nerve: CN VIII motor nerve: CN III, VI result: Fast phase in direction of head movement (in peripheral vestibular lesion - fast phase AWAY from side of lesion)