66b47176-e392-4b2d-91cf-71bb58169c6b.pdf

Basal ganglia 1. Know the different nuclei in the basal ganglia. • Caudate Nucleus: c-shaped structure that follows the lateral ventricle o Receives input from * Cortical association regions (BA 5 and 7) * Frontal eye field (BA 8) * Limbic regions of cortex Neostriatum o Integrated cortical inputs C...

Basal ganglia 1. Know the different nuclei in the basal ganglia. • Caudate Nucleus: c-shaped structure that follows the lateral ventricle o Receives input from * Cortical association regions (BA 5 and 7) * Frontal eye field (BA 8) * Limbic regions of cortex Neostriatum o Integrated cortical inputs Caudate Nucleus o Cognitive aspect of movement & Putamen o Eye movement Lentiform o Emotional correlates of movement Nucleus • Putamen: adjacent to GP Putamen & o Receives input from Globus Pallidus * M1 * S1 * Primary somatosensory regions o Movement regulation (motor functions) • Globus Pallidus (GP): major output from BG via thalamus o GP internus (medial) and GP externus (lateral) • Subthalamic Nucleus (STN): below thalamus • Substantia Nigra (SN): located in MB o Pars Compacta (SNpc): output mainly DA (collection of cluster cells) o Pars Reticulata (SNpr): output mainly GABA (network) 2. Know the functions of the basal ganglia. • Role in voluntary movement • No direct input or output to SC • Feedback mechanism to CC for initiation and control of response • Output mediated through thalamus to dampen excitatory input to CC • Motor functions o Movements initiated in cortex → BG modulates motor programs * Ex: bringing hand to mouth o Ensures only intended programs are activated • Cognitive Functions o Via cortical loops in prefrontal association cortex and limbic system o Important in selecting cognitive, executive, or emotional programs o Important in motor learning (rewards) 3. Know the projections from the substantia nigra pars compacta and pars reticulata. • SNpc: wants movement to happen o Direct pathway: excites neostriatum via D1 receptors (DA) o Indirect pathway: inhibits neostriatum via D2 receptors (DA) • Neostriatum → SNpr → superior colliculi (MB) → eye movement o Output pathway from BG o Efferents from SNpr are GABAergic o Inhibit unwanted eye movements by inhibiting superior colliculi and thalamus o For movement to occur, the thalamus and superior colliculi need to be released from tonic inhibition 4. Know the direct and indirect pathways completely and the associated neurotransmitters. Know how the two pathways work in sync. Know the role of dopamine. • Role of DA: ensures balance between direct and indirect pathways 5. Know how the pathways are affected in Parkinson’s and Huntington’s Disease. Parkinson’s Disease • Nigrostriatal pathway excites direct pathway and inhibits indirect pathway • Loss of input tips balance in favor of indirect pathway - GPI neurons are abnormally active, keeping thalamic neurons inhibited - Without thalamic input, motor cortex isn’t as excited → cortex is less able to execute motor plans in response to patient’s volition Huntington’s Disease • GPE more active because absence of normal inhibitory input • This activity  excitatory output of STN to GPI • Inhibitory output of GP is  • UMN can now be activated by inappropriate signals → motor programs with no control → choreic and ballistic movements • Balance tipped in favor of direct pathway 6. Describe Parkinson’s disease and Huntington’s disease. • Parkinson’s Disease: progressive degenerative disease characterized by loss of dopaminergic cells in SN o Clinical features * Bradykinesia ◌  movement velocity and amplitude, impaired reaction time * Resting tremor * Rigidity * Postural instability * Abnormal postural reflexes ◌ Masked face/hypomimia and festination/shuffling gait * Stooped posture * Migrographia: small handwriting * Saccades  in frequency and amplitude o Therapies * Medication: levodopa (S/E: dyskinesia) * Neurosurgery: deep brain stimulation of subthalamic nuclei, VL, and VA * STN: bradykinesia, tremor, and rigidity * Physical Therapy ◌  activity to ≥ 2.5 hours/week → slow the decrease in quality of life ◌ Safe exercises to slow progression ◌ Rehab of walking, balance, posture, mobility, and fear of fall ◌ LSVT Big and LSVT Loud • Huntington’s Disease: selective degeneration of striatal neurons in indirect pathway o Chorea: involuntary, continuous movement of body (extremities and face) o Balance tipped in favor of direct pathway → hyperkinetic movement disorder o Motor, cognitive, and emotional disturbances Cerebellum 1. Know the functional divisions of the cerebellum and their roles. • Vestibulocerebellum: input from vestibular system o Important for postural control o Status of head region * Vestibulo-ocular Reflex (VOR): control of eyes and position of head o Flocculonodular lobe • Spinocerebellum: input from SC o Status of axial musculature (muscle tone) o Axial muscles degree of flexion/extension at any given point o Vermis: eye movements and control of proximal and axial muscles o Anterior lobe and vermal regions of posterior lobe • Cerebrocerebellum: highly skilled movements (ex: speech) o Planning, organizational, and coordinating aspects of motor response o Linked closely with CC CLL control of CC is o Most developed and largest contralateral o Posterior lobe CLL control of body is 2. Know the 3 cerebellar peduncles. ipsilateral • Superior: efferent pathway (send info OUT of CLL) R CC → L CLL → L body o Arise from deep CLL nuclei L CC → R CLL → R body o Project to * Red nucleus (rubrospinal tract): flexor muscle activation * Superior Colliculi (MB): eye/hand coordinated movements * VL in thalamus → M1 and PMA for coordination of voluntary movement • Middle: afferent pathway (RECEIVES info into CLL) o Cell bodies that give rise to this pathway are at the base of pons * Pontine nuclei o Transverse Pontine Fibers: axons from pontine nuclei that cross midline to opposite CLL cortex (R CC → L CLL cortex) o 20 million axons per middle CLL peduncle • Inferior: afferent AND efferent projections (input/output) o Largest component includes fibers arising from inferior olivary nucleus o Project (output) to vestibular nuclei and reticular formation (RF) o Afferent input from * Vestibular nuclei * Spinal nuclei: nucleus dorsalis of Clarke and cuneate nucleus * Trigeminal complex: face proprioception * BS nuclei: visual and auditory signals 3. Understand the cortical, brainstem and spinal cord projections to the cerebellum. • Cortical projections→ pontine nuclei → cross at middle peduncle → CLL cortex and deep CLL nuclei o Motor and PMA for motor control o PPC for sensory-motor integration o Temporal and occipital cortex for visuomotor coordination and auditory signals • BS projections to CLL o CC → red nucleus → Inferior Olivary Nucleus→ inferior peduncle → CLL cortex and deep CLL nuclei * Role in learning and memory * SC inputs: cutaneous afferents, joint afferents, and muscle spindles o Superior and inferior colliculi → pontine nuclei → CLL cortex & deep CLL nuclei * Visual and auditory info o Vestibular axons from 8th CN and vestibular MO → vestibulocerebellum o RF in medial white matter of SC * Mediate spinal reflexes * Acts on gamma motor systems (extensor muscles) * Relay for sensorimotor cortical inputs to CLL * Projects to vermal region of anterior and posterior CLL lobes • SC projections → inferior peduncle → CLL cortex and deep CLL nuclei o Proprioceptive axons via nucleus dorsalis of Clarke and cuneate nucleus → spinocerebellum → monitor body position and motion of body o Vestibular and proprioceptive inputs remain IPSILATERAL from origin 4. Know the deep cerebellar nuclei and their efferents. • Most of CLL projects to deep CLL nuclei prior to reaching target • VL in thalamus is a major relay target from CLL → motor cortex • Deep CLL Nuclei: 4 major deep nuclei purkinje cells in vermal region (spinocerebellum and vestibulocerebellum) purkinje cells in paravermal region (spinocerebellum) FASTIGIAL NUCLEUS INTERPOSED NUCLEUS (emboliform and globose nuclei) vestibular nuclei and RF CN nuclei in BS and extensor MN in SC (vestibulospinal and reticulospinal tracts for balance, posture, and vestibulo-ocular regulation) purkinje cells in cerebellar hemispheres (cerebrocerebellum) M1 and PMA DENTATE NUCLEUS VL in thalamus VL in thamalus superior CLL peduncle (CROSS) motor and premotor cortex DENTATE NUCLEUS CST for planning, coordination, and execution of motor response CLL cortex red nucleus SC (rubrospinal tract for control of flexor MN) 5. CLL layers, characteristics of the Mossy & Climbing fibers, and Purkinje cells. • CLL cortex layers: granular (inner) → purkinje cells → molecular (outer) o Purkinje Cells: destination of AFFERENT pathways to CLL cortex * Receives input from large number of parallel and climbing fibers * Have GABAergic inhibitory output to deep CLL nuclei * Only output cells of CLL cortex * Inhibition modulates excitation from mossy and climbing fibers that branch to deep CLL nuclei • 2 kinds of AFFERENTS to CLL o Mossy Fibers: axons from pontine & most CLL inputs in BS & SC * Synapse onto granule cells * 1 mossy can excite many granule cells * Granule cells give rise to parallel fibers which have excitatory synapses onto purkinje cells ◌ Mossy → granule cells (parallel fibers) → purkinje cells o Climbing Fibers: arise from inferior olive * Direct synapse (excitatory) onto purkinje cells (1000 synapses) * 1-to-1 relationship with purkinje cell 6. Describe cerebellar disorders and the relationship with somatotopy of the cerebellum. • Ataxia: errors in range, rate, force, and direction of movement → loss of muscle coordination o Errors in movement are ipsilateral to lesion o Asynergia: loss of coordination o All symptoms due to disruption of feedback circuits between CLL cortex and CC that governs movements of distal musculature • Gait Ataxia: lesion of flocculonodular lobe or vermal region of anterior and posterior lobes o Wide and slow gait o Tendency to fall on side of lesion o Common in alcoholic CLL degeneration affecting anterior lobe o All symptoms due to a disruption of feedback circuits involving vestibulocerebellum and/or spinocerebellum and their connections with the fastigial nucleus and its output pathways to vestibular nuclei, RF, and SC • Somatotopic Organization o Lesion of vermis and spinocerebellum: gait or truncal ataxia o Lesion of CLL hemispheres * Limb ataxia * Decomposition of movement * Asynergia * Dysdiadochokinesia * Intention Tremor 7. Know the terms that were presented in the slides pertaining to cerebellar disorders such as dysmetria, ataxia etc. • Dysmetria: undershooting/overshooting • Post-pointing: overshooting errors while performing a movement • Dysdiadochokinesia: inability to perform alternating pronation/supination • Intention Tremor: tremor while performing movement • Nystagmus: vermis lesion → uncontrolled, repetitive eyeball movement Somatosensory system 1. Characterize the sensory receptors that mediate sensations elicited by touch, vibration, pressure, proprioception, pain, and temperature. • Meissner’s Corpuscle: respond to touch, form, and texture o Beneath epidermis of fingers, palm of hand, plantar surface of foot, and toes (glabrous skin) o Low threshold and rapidly adapting o Sensitive to touch and vibration < 100 Hz o Detect skin motion (slippage between skin and object in hand) • Merkel’s Receptor/Disc: respond to pressure o Low threshold and slowly adapting o Modified epidermal cells o On glabrous skin: dense in fingertips and lips o Sensitive to pressure stimuli, edges, points, corners, and curvatures o Help in discriminating objects o When constant force is applied o Indicates sharpness of object o Memory allows us to identify object o Blind people rely on these to read braille • Pacinian Corpuscle: respond to deep pressure and vibration o Located deep in dermis layer of hairy and glabrous skin o Bare nerve terminal of myelinated peripheral axon of primary sensory neuron at center of corpuscle o Low threshold and rapidly adapting o Sensitive to rapid indentation of skin caused by  frequency vibrations (100-400 Hz) • Ruffini’s Ending: information about magnitude and direction of stretch o Located in dermis layer of hairy and glabrous skin o Bundles of collagen fibrils connected with fibrils of dermis o Low threshold and slowly adapting o Sensitive to stretching of skin 2. Know the classification of nerve fibers. • Myelinated o Ia (A𝜶): annulospiral endings of MS * Largest diameter and fastest o Ib (A𝜶): fibers from GTO * Large diameter and fastest o II (A𝜷): flower-spray endings of MS and cutaneous tactile receptors * Medium diameter and speed o III (A𝜹): fibers conducting crude touch, temperature, and FAST pain * Small diameter and slow • Unmyelinated o IV (C): fiber carrying SLOW pain and temperature sensations * Smallest and slowest 3. List the slow and rapidly adapting receptors and describe receptive fields, two-point discrimination and lateral inhibition. • Rapidly Adapting (phasic): respond maximally but briefly to stimuli o Response  if stimuli is maintained o Meissner’s Corpuscle and Pacinian Corpuscle • Slow Adapting (tonic): keep firing as long as stimulus is present o Merkel’s Receptor and Ruffini’s Ending • Receptive Fields: space in which sensory receptor is located and where it produces transduction of stimuli o Size determines resolution with which you can perceive objects o Important for tactile, visual, and auditory acuity o Large field: Pacinian Corpuscle and Ruffini’s Ending (acuity) o Small field: Meissner’s Corpuscle and Merkel’s Receptor ( acuity) • Two-Point Discrimination: minimal distance required to perceive 2 simultaneously applied stimuli as distinct o We discriminate between 2 points using lateral inhibition * Excitatory and inhibitory signals * Neurons in center inhibit activity of neighboring neurons via interneurons 4. Understand the stretch reflex circuity and know the afferents and efferents. Know reciprocal inhibition, role of gamma motor neurons and supraspinal control. • Muscle Spindles: present in skeletal muscles to sense changes in muscle stretch/length o  in muscles controlling fine movements * Hands, speech organs, extraocular muscles o Each contains 8-10 specialized muscle fibers (intrafusal) * Nuclear Bag Fibers: bag-like dilation at center * Nuclear Chain Fibers: smaller and shorter single row of central nuclei o Efferents (SC → muscle) * Extrafusal Fibers: surrounding skeletal muscle fiber innervated by alpha MN * Intrafusal Fibers: at contractile terminal end of MS innervated by gamma MN o Afferents (muscle → SC) * Annulospiral Ending: group Ia ◌ In central part of nuclear bag and chain fibers ◌ Activated by brief stretch or vibration of muscle and sustained stretch * Flower-spray Endings: group II ◌ On ends of nuclear bag and chain fibers ◌ Activated by sustained stretch • Myosynaptic/Stretch Reflex: monosynaptic (afferent directly synapses on efferents (2)) stretch of muscle (quads) Reciprocal Inhibition stimulate MS in quads group Ia afferents from MS make excitatory synapse with an inhibitory interneuron in SC activates Ia afferents inhibitory interneuron makes inhibitory synapse with alpha MN innervating antagonist afferents carry impulse to SC and synapse with aplha MN (efferents) reciprocal inhibition of antagonist (knee flexors) alpha MN synapse on extrafusal fibers on muscle causing contraction (knee extension) o Role of gamma MN: present in SC and intermingled with alpha MN * Innervate intrafusal fibers * Activation → intrafusal fibers isometric contraction → spindle discharges * Primary function: reset spindle mechanism and  likelihood of Ia afferents discharging o Supraspinal Control * Gamma MN under descending pathways control ◌ Projections from CC and reticulospinal tracts (RST) * Excitation of gamma MN →  muscle tone → facilitates stretch reflex * Medial RST:  muscle tone and facilitates reflex * Lateral RST: inhibits gamma MN and inhibits reflex 5. Describe the role of the Golgi tendon organ and its role in mediating non-conscious proprioceptors. • Golgi Tendon Organs (GTOs): sensory receptors at junction of muscle and tendon o Sense changes in muscle tension o AKA Myotatic Reflex (protective mechanism) active contraction of muscle GTO activates volley produced in afferent Ib fibers Ib make excitatory synapse with interneurons that inhibit alpha MN net effect:  period of muscle contraction 6. Know the differences between fast pain and slow pain. • Pain stimulates nociceptors • Mechanical Nociceptors (A𝜹): sharp, pricking sensation and FAST pain • Thermal Receptors(A𝜹): slow, burning, cold, sharp, prickling sensations • Polymodal (C): hot and burning sensation, cold, mechanical stimuli, and SLOW pain 7. Understand the flexion withdrawal reflex and crossed extensor reflex circuitry. • Flexion Withdrawal Reflex noxious stimuli applied at skin sends afferents to SC activation of polysynaptic pathways in SC contraction of IPSILATERAL flexors and relaxation of extensors flexion of agonists and relaxation of antagonist • Crossed Extensor Reflex afferents send collaterals via anterior commisure to OPPOSITE side synapse with alpha MN that innervate CONTRALATAERAL flexors and extensors reflex causes relaxation of contralateral flexors and contraction of contralateral extensors Peripheral nervous system ** ** 1. Know the Henneman’s size principle, spatial and temporal summation in motor units. • Henneman’s Size Principle: motor units recruited in order of o Smallest and weakest→ largest and strongest o Slow twitch (type I) → Fast twitch (type II) * Type I → type IIa → type IIb • Temporal Summation: motor unit firing frequency (recruited have to work harder) • Spatial Summation: recruitment of more motor units 2. Compare & contrast different types of neuropathies (pathologies of the peripheral nerve) • Mononeuropathy o Physical trauma: one-time event (stretch or compression) o Overuse: stretch or compression, vascular insult o Ex: carpal tunnel syndrome • Polyneuropathy o Disease: autoimmune (GBS), metabolic (diabetes), hereditary, infectious o Toxins (too much alcohol, chemo, lead poisoning) o Involve multiple nerves o Classified in many ways * Axonal degeneration vs * Distal vs proximal vs diffuse vs segmental demyelination * Symmetric vs asymmetric * Motor vs sensory * Acute vs chronic o Mononeuropathy Multiplex: immune & susceptible to compression syndrome 3. Review the Seddon and Sunderland classifications of nerve injury. • Seddon: 3 classifications o Neurapraxia (I): conduction block * Physiologic loss of function usually due to demyelination * Axon and cell body are intact (no degeneration) * Paralysis or sensory disturbances often partial * Recovery is rapid and complete * Etiology: pressure or stretch o Axonotmesis (II): axon damage * Axon and cell body are separated (Wallerian degeneration) * Connective tissue structure intact ◌ Recovery possible and prognosis is ~good ◌ Regeneration: 1mm/day or 1in/month * Etiology: stretch or compression (most common), toxic, autoimmune o Neurotmesis (III): complete section of nerve trunk (all axons and connective tissue) * All factors as axonotmesis + connective tissue involved * Prognosis is poor: surgery is required * Etiology: laceration, severe contusion, severe stretch • Seddon Groups Neurapraxia Sunderland: 5 degrees Sunderland Axon Endoneurial Perineurium Epineurium Nerve Fibrillation Degrees tube conduction potentials distal to on EMG injury 1st Intact Intact Intact Intact Present Absent Axonotmesis 2nd Affected Intact Intact Intact Absent Present 3rd Affected Affected Intact Intact Absent Present Neurotmesis 4th Affected Affected Affected Intact Absent Present Neurotmesis 5th Affected Affected Affected Affected Absent Present ** 4. Know the differences between axonal and demyelinating polyneuropathies (slide 37 – 40). Axonal Demyelinating Distribution of deficits Distal (stocking and glove) Diffuse (proximal and distal) Length dependent Segmental (multifocal) Symmetrical Spotty Sensation Sensory > motor Motor and sensory Pain, temperature, light touch, Mild: proprioceptive and vibration vibration loss Distal areflexia Sensory ataxia and areflexia Autonomic involvement Yes, with small fiber loss Only in GBS or autoimmune dysautonomia Conduction velocity Normal or mild slowing Marked slowing Amplitude Affected Not as affected Conduction block No Yes, with acquired demyelination CSF protein Normal Elevated Causes Toxic, disease, hereditary Autoimmune, hereditary Prognosis Poor to good Good (for the most part) Onset Acute: ischemia, toxin, critical Acute: GBS illness Subacute: chronic inflammatory Subacute: toxic, nutritional, demyelinating polyneuropathy paraneoplastic (CIDP), monoclonal gammopathy Chronic: metabolic, hereditary CNS Involvement Recovery Examples Occasional (toxic: dorsal columns affected) Slow Axon regrowth guided by Schwann cell and basal lamina tubes Lead poisoning Diabetes Alcohol Charcot Marie Tooth Type II (HMSN type II) Chronic: hereditary, CIPD, monoclonal gammopathy Rare Hereditary metabolic disorders Rapid Schwann cell proliferation and remyelination with shortened internodes GBS (AKA Acute Inflammatory Demyelinating Polyneuropathy) CIPD (chronic) Charcot Marie Tooth Type I (HMSN type I) ** 5. Discuss prognostic factors for nerve recovery (axon regeneration) • Connective tissue structures • Distance to target organs • Age • Distance from cell body • General health 6. State the reaction of the neuron to injury. • Severing an axon → proximal segment (connected to cell body) and distal segment o Synaptic transmission in distal segment is lost rapidly o Distal segment undergoes Wallerian Degeneration * Occurs over 1-2 months depending on location o Cell body nucleus swells and moves eccentrically: chromatolysis * Because of retrograde transport o Cells that have synaptic connections with injured neurons degenerate * Ex: muscle cells 7. Use clinical presentation and exam findings to localize a neuropathy. • History o Weakness: be specific (myotome, peripheral nerve) o Sensory loss: be specific (dermatome, peripheral nerve) o Balance o Where? Proximal, distal, diffuse • Medical History: if diabetes present, for how long and is it under control? • Conditions associated with polyneuropathy o Diabetes o Hypothyroidism o Alcohol abuse o Cirrhosis o Autoimmune conditions o Vitamin deficiency (B1, B6, B12, E) o Bacterial or viral infeciton o Chemo or drugs to treat HIV o Toxin exposure o Family history • Conditions associated with entrapment neuropathies o Any underlying condition above o Very specific and related to occupational/ recreational exposure 8. Know how the muscle reinnervates. • 2 processes that can occur together or separately • Collateral Sprouting: healthy axons adopt denervated muscle fibers o End result is a large motor unit with many muscle fibers per axon o Fine control may be sacrificed depending on function of motor units o Affects force gradation with recruitment • Axon (Direct) Regeneration: original injured axon regrows to reach muscle fiber Auditory System and Vestibular System 1. Describe anatomy and functions of external, middle, and inner ear. • External Ear: collects sound waves and focuses it on tympanic membrane o Concha: collects sound o Pina o External Auditory Meatus: opening • Middle Ear: amplifies pressure o Tympanic membrane → bones vibrate → oval window → inner ear o Converts sound waves in air into waves in fluid located in inner ear (high impedance) o Amplify sound pressure 200-fold * Tympanic membrane has large diameter and focuses sound to small diameter oval window through lever action of bones o Malleus, Incus, and Stapes: 3 bones with joints between them o Tensor Tympani and Stapedius Muscles: contract and  amount of sound energy transmitted to inner ear • Inner Ear: performs series of biomechanical processes (break signal into freq., amp.) o Cochlea: transmits pressure waves of sound into nerve impulses * Mechanical frequency analyzer: decomposes complex acoustic waveforms into simpler form * Organ of Corti: sensory area of cochlea located on basilar membrane * Basilar Membrane: shows tonotopy ◌ Hair Cells: sensory receptors for sound that are bent by shearing motion of tectorial and basilar membranes ◌ Stereocilia: tiny processes that bend when voltage changes with tips embedded in tectorial membrane and bodies in basilar membrane 2. Understand the mechanisms underlying an action potential mediated by the hair cell. hair cells deflect K+ mechanically-gated channels open K+ influx depolarization Ca2+ channels open in soma Ca2+ influx NT release onto auditory nerve and K+ efflux Outer Hair Cells • Termination mostly from EFFERENT axons that arise from cells in superior olivary complex • Attached to tectorial membrane • Depolarize with shearing force • Sharpen frequency resolving power by actively contracting and relaxing (change in tectorial stiffness) Inner Hair Cells • Actual sensory receptors • 95% auditory nerve fibers to the brain arise from this cell • Depolarize with endolymph movement 3. Describe the mechanism of sound conduction and tonotopy sound causes tympanic membrane to vibrate oscillatory movement of stapes against oval window pressure waves in perilymph in scala tympani and scala vestibuli Tonotopy in Basilar Membrane - Base hair cells: high frequency - Apex hair cells: low frequency Tonotopy maintained throughout auditory pathways vibration of basilar membrane (move UP) upward displacement of basilar membrane causes shearing force of tectorial membrane Tonotopy in A1 (BA 41, 42) - Base of cochlea: high frequency - Apex of cochlea: low frequency lateral displacement of stereocilia and kinocilium K+ influx from endolymmph (more K+ outside stereocilia) hair cells depolarize Ca2+ influx into soma release of excitatory NT into afferent nerve terminal @ base of hair cell opens Ca2+ - activated K+ channels in basal region of hair cell K+ efflux 4. Describe the auditory pathways. primary auditory cortex (A1) Superior Olivary Nucleus project to MGN (4th ON) in thalamus Receives BILATERAL input from cochlear nuclei synapse with neurons in inferior colliculi (3rd ON) in MB Localizes sound via 2 mechanisms Below 3 kHz: interaural time difference Above 3kHz: interaural intensity cross in pons cochlear nerve synapses with dorsal and ventral cochlear nuclei (2nd ON) in rostral MO central processes of bipolar neurons in spiral ganglia(1st ON) project to cochlear nerve 5. Describe the clinical disorders associated with the auditory system. • Conduction Deafness: damage to external or middle ear (most common) o Lowers efficiency at which sound is transferred to inner ear o Causes: chronic middle ear infection or outgrowth of stapes o Diagnose: weber test * Affected side will be perceived as being louder and receive sound only through bone conduction o Treat: hearing aids to amplify sounds • Sensorineural Deafness: damage of auditory nerve o Impairs transduction of sounds (can’t form action potentials) o Diagnose: weber test * Sound louder on intact side * Affected ear can’t convert sound to neural signals o Treat: cochlear implants to create neural impulses to auditory nerve 6. List the anatomy and physiology of different components of the vestibular system (otolith, semicircular canals, otolithic membrane etc.) • Otolith Organs o Utricle: detects linear acceleration in HORIZONTAL plane * Forward acceleration and deceleration * Detects lateral flexion of head o Saccule: detects linear acceleration in VERTICAL plane * Forward and backward head tilt * Detects neck extensions and flexion * Detects static head position relative to gravity o Semicircular Canals: detect rotational acceleration of head * 3 canals: superior, posterior, and horizonal * Crista: sensory epithelium that contains hair cells that displace when head is rotated in plane specific to one of the canals * Cupula: gelatinous mass that displaces hair cells ◌ When head moves in a certain plane, inertia of endolymph generates force across cupula ◌ This force moves cupula AWAY from direction of head movement, leading to displacement of hair cells in crista o Hair Cells: in utricle, saccule, and ampulla of semicircular canals * Respond to motion and create electrical signals to CN VIII * Stereocilia move toward kinocilium → opens mechanically-gated transduction channels → depolarization of hair cells → NT released to vestibular nerve • Otolith o Otolith Membrane: embedded with otoconia o Otoconia: crystals of calcium carbonate o Macula: sensory epithelium that consists of hair cells and associated supporting cells * Linear acceleration/deceleration → movement of cilia and otolithic membrane o Striola: depression in membrane where polarity changes Saccule Vertical (y-axis) Utricle Horizontal (x-axis) 7. Understand the VOR, VCR and VSR. Vestibulo-Ocular Reflex (VOR) excites L medial rectus inhibits R medial rectus oculomotor nucleis in MB excite R lateral rectus inhibits L lateral rectus medial longitudinal fasciculus in pons abducens nucleus in pons medial vestibular nuclei in MO scarpa's ganglion L horizontal semicircular canal activated VOR Mechanism for producing eye movements that counter head movements, thus permitting the gaze to remain fixed on a particular point VSR (solid lines) Extension of body Upright posture VCR (dotted lines) Head movement (in Cx region of SC) From fastigial nuclei in CLL ex: turn head to L 8. Know how the vestibulospinal system is involved in the maintenance of balance and posture are mediated. (PROJECTIONS OF VESTIBULAR NUCLEI) • CN III, IV, and VI → mediate adjustment of eyes in response to change in posture • Ventral horn cells in cervical SC →changes in position of head • Motor neurons of cervical and lumbar SC → powerful excitation of extensor muscles • Vestibulocerebellum → modulation of descending pathways from vestibular nuclei and RF, which control posture and muscle tone 9. List the clinical disorders associated with the vestibular system. • Nystagmus: can be caused by BS or CLL flocculonodular lobe lesion o Vestibular system role in normal VOR affected * Normal: initial slow phase of eye movement when eyes are fixed on an object when head is rotated in opposite direction • Vertigo: sensation of turning/rotation in space in the absence of actual rotation o Caused by debris from otolithic membrane that may adhere to cupula, making it more sensitive to angular movement • Motion Sickness: conflicting signals from eyes and vestibular system sent to CNS Visual system and visual pathways 1. Know the anatomy of the eye. • Inner Tissue Layer: retina (projects to occipital cortex) o Contains neurons that are light sensitive (photoreceptors) o Capable of transmitting signals to central targets o Inners surface of retina * Fovea: lights focuses on the center * Optic Disc: AKA blind spot because it has no photoreceptors * Macula: responsible for central vision (PCA and MCA) • Middle Tissue Layer: uveal tract o Choroid: important for nourishing photoreceptors of retina o Ciliary Muscle: ring of tissue that encircles the lens o Iris: colored portion of eye o Pupil: central opening of eye that constricts and dilates (window) • Outer Tissue Layer o Sclera: white and tough fibrous tissue o Cornea: transparent structure at the front of the eye permitting light rays to enter • Aqueous Humor: between lens and cornea o Clear, watery liquid supplying nutrients to cornea and lens o Produced by ciliary processes in posterior chamber o Fluid of anterior chamber replaced continuously • Vitreous Humor: between lens and retina o Thick, gelatinous substance o Contains phagocytes that remove debris that might interfere with light transmission o Floating debris can cause shadows on retina in older individuals 2. Understand the functions of the cornea and lens. • Transparent (like glass) responsible for bending light o Focused images on retina depend on this • Alterations in cornea or lens reduce transparency and seriously affect vision o Leads to cataracts: opacities of lens * Accounts of ½ of world blindness * By 70 years old, most people lose some transparency of lens 3. Know the structures that are responsible for near versus far accommodation. • Accommodation: dynamic changes in refractive power of lens o Cornea does most of bending of light • Far: zonule fibers contract and ciliary muscles relax → lens is flattened • Near: ciliary muscles contract and zonule fibers relax→ lens is round • Shape of the lens determined by: o Elasticity of lens which keeps it round o Tension of zonule fibers (suspensory ligament) • Presbyopia: accommodation problems with age as lens loses elasticity o  in max curvature when ciliary muscles are contracted o Focus point must be farther away o Near vision becomes impossible 4. Know the refractory errors of the eye. • Myopia: nearsightedness o Corneal surfaced is too curved o Eyeball is too long o Focus doesn’t hit the retina perfectly o Corrected by concave lens • Hypermetropia: farsightedness o Eyeball is too short o Refractory system too weak o Focus point is “behind” retina o Corrected by convex lens 5. Know the pathophysiology of glaucoma and macular degeneration. • Glaucoma:  pressure because of failure to adequately drain aqueous humor • Macular Degeneration: progressive loss of central vision o Leading cause of vision loss over 55 o Degeneration of photoreceptors 6. Know the types of neurons in retina. Know the function of horizontal and amacrine cells. • Types of neurons in retina o Neuron Chain: photoreceptors → bipolar cells → ganglion cells * Bipolar Cells: interneurons between photoreceptor and ganglion cells that generate graded potentials * Ganglion Cells: integrates electrical activity from bipolar and amacrine cells ◌ Gives rise to axons that form optic nerve ◌ Only cell class in retina that fires action potentials o Modulate lateral vision, luminance, & contrast of light: horizontal & amacrine cell • Horizontal Cells: mediate lateral interactions between photoreceptors and bipolar cells • Amacrine Cells: mediate lateral interactions between bipolar cells and ganglion cells 7. Compare the differences between rods and cones. Know function of pigment epithelium. • Photoreceptors: light sensitive elements that contract horizontal and bipolar cells that generate graded potentials o Rods: extremely sensitive to light * Low spatial resolution * Enable dim light and night vision * Contain rhodopsin o Cones: relatively insensitive to light * Very high spatial resolution * Enable color vision * Contain cone-opsin • Pigment Epithelium:  scattering of light that enters eye o Contains melanin o Important for metabolic sustenance and oxygenation 8. Understand light vs dark-induced changes in photoreceptors and the sequence of events in phototransduction. LIGHT-INDUCED CHANGES IN THE DARK LIGHT-INDUCED CHANGES IN THE LIGHT cGMP is in high concentration inside the cell cGMP concentration is reduced once light stimulates the region binds to Na+/Ca2+ channels keeping them open Na+/Ca2+ channels close allows Na+/Ca2+ influx keeping membrane relatively depolarized receptor hyperpolarization (K+ efflux) PHOTOTRANSDUCTION light stimulates rhodopsin or cone-opsin transducin activated (G protein) phosphodiesterase activates (PDE) Phototransduction Conversion of light to electrical signals PDE catalyzes cGMP  of cGMP closes Na+/Ca2+ channels influx of Na+ reduced hyperpolarization 9. Generally, know the differences between on-center and off-center ganglion cells. • Ganglion Cells: respond to stimulation of a small patch of the retina (receptive field) that CAN produce action potentials (AP) o Changes in light intensity ( or ) are conveyed by  frequency of AP train • On-center:  discharge rate to luminance  in receptive field center o Seeing objects brighter than background (ex: moon at night) o If deactivated: can’t see objects that are brighter than background • Off-center:  discharge rate to luminance  in receptive field center o Seeing objects darker than background 10. Know how graded potentials eventually form action potentials in ganglion cells. 11. Know the pathway of the optic nerve. • Axons in the optic nerve run a straight course to the optic chiasm o 60% cross → thalamus and MB targets on opposite side o 40% stay uncrossed → thalamus and MB targets on same side o Once past the optic chiasm, ganglion cell axons on each side form the optic tract, which contains fibers from both eyes • Optic nerve → reach optic chiasm and cross → optic tract 12. Know the central projections of the retinal ganglion cells. • Ganglion cell axons exit the retina through the optic disk and bundle together to form the optic nerve o Optic Disk: circular, whitish region in retina nasal part that has no photoreceptors, is insensitive to light, and produces the blind spot • Hypothalamus: regulates circadian rhythms (day/night cycles) • Pretectum: reflex control of pupil and lens (around MB) • Superior Colliculus: orients movements of head and eyes (MB) • Striate (occipital) complex: principal pathway to V1 that leads to perception • Targets of Ganglion Cell Axons: retinogeniculostriate pathway o LGN of thalamus → IC optic radiation → primary visual cortex 13. Know the pupillary light reflex circuitry. • Pretectum: coordinating center for pupillary light reflex o  diameter of pupil when light falls on retina • Clinicians use this reflex to examine the integrity of visual apparatus, motor outflow to pupillary muscles, and central pathways mediating the reflex • Direct Light Reflex: eye light is being shined on constricts • Indirect Light Reflex: eye light isn’t being shined on constricts • Constriction happens in both eyes because of bilateral innervation PUPILLARY LIGHT REFLEX ganglion cell axons target neurons in pretectum afferents from both eyes ativate pretectum pretectum projects BILATERALLY to edingerwestphal nuclei (EWN) efferent projections from EWN (CN III nucleus) go to ciliary ganglion neurons in ciliary ganglion innervate constrictor muscles in iris 14. Understand the visual field defects. Akinetopsia • Rare motion blindness • Stroke in MT region 15. Know the differences between the dorsal and ventral streams. M ganglion cells P ganglion cells • • magno LGN parvo LGN V1 V1 dorsal stream (critical to evaluating motion) ventral stream (high spatial resolution) temporal and parietal lobes inferotemp oral surface M Cells: larger receptive fields and respond transiently to visual stimuli P Cells: respond in a sustained fashion and transmit information about color respond to motion responds to shapes, colors, objects, and faces