Taste & Olfaction The Chemical Sense

Introduction What are the special senses o Taste and olfaction Why study them o Mostly related to quality of life but have some clinical significance The Gustatory System Clinical Terms Hypogeusia: below the normal sense of taste Parageusia/dysgeusia: altered sense of taste Ageusia: absence of the sense of taste Tastant: gustatory stimulus Taste Receptors Four (5?) Types o Sweet: G protein coupled ligand mediated receptors o Salty: Na+ entry via Na+ channels o Sour: blocking of apical K+ channels, H+ entry via a+ channels o Bitter: some by blocking of apical K+ channel; others by G protein coupled receptors o Umami: flavor of MSG? Receptors contained within taste buds (40-60 receptors/bud) Turnover rate of 10-14 days Arise from basal cells within taste bud Are NOT neurons Taste Buds (Receptors) Taste sensory organ Taste bud consists of o Receptor cells o Basal cells o Support cells Innervated by afferent fibers

Taste Bud Types Lingual taste buds are located on three different kinds if papillae: o Fungiform: anterior 2/3 of the tongue; responds mostly to sweet, salty, and some sour tastants (CN VII) o Foliate: posterior edge of the tongue; responds mostly to sour tastants (CN VII) o Circumvallate: posterior 1/3 of the tongue, responds mostly to bitter tastants (CN IX) Extralingual tastebuds are located on: o soft palate (CN VII), o oral pharynx (CN IX), o laryngeal pharynx, larynx, upper esophagus, and epiglottis (CN X)

Taste Transduction

when the second messenger triggers a signal there is a calcium dependent release of an unknown transmitter which causes a threshold stimulus and an AP generated from the afferent neuron into the CNS

Peripheral Pathways

in the brainstem, in the dorsolateral aspect of the medulla taste info from the anterior 2/3 of the tongue and the soft palate are carried along CN VII, the cell body is in the geniculate ganglion, and the synapse is made in the solitary tract and nucleus taste info from the posterior 1/3 and the oral pharynx are carried in by CN IX, cell body is in the petrosal ganglion and it synapses in the solitary tract and nucleus

taste info from the epiglottis, laryngeal pharynx, larynx, upper esophagus are carried in by CN X, cell body is in the nodose ganglion and it synapses in the solitary tract and nucleus general sensation of pain and temperature from the tongue is carried by CN IX and X, the cell bodies are in the petrosal and nodose ganglion but it synapses in the caudal aspect of the solitary nucleus (special sensation of taste synapses in the rostral aspect of the solitary nucleus)

Central Pathways

the first order neuron will synapse in the solitary nucleus, while the second order neuron will ascend through the tegmentum of the brainstem as central tegmental tract and synapse in the thalamus in the ventral posterior medial nucleus (nucleus VPM); the third order neuron will leave VPM through the internal capsule and up to post central gyrus

The Olfactory System Terminology Rhinencephalon: portion of the basal forebrain mediating olfaction Euosmia/normosmia: normal sense of smell Hyposmia: below normal sense of smell Anosmia: absence of the sense of smell Odorant: olfactory stimulus Phylogeny The rhinencephalon predominates in lower vertebrates

Embryology The olfactory bulb and tracts (5) arise from the telencephalon through the process of evagination o Why it doesnt pass through the thalamus (which is diencephalon) Olfactory Epithelium Yellowish patch of epithelium in upper nasal cavity bathed in mucus Consists of o Receptor cells Tight junctions between the support cells and olfactory receptor neurons o Sustenacular (support) cells o Basal cells stem cells, (one of two areas of brain besides hypothalamus which have stem cells), become receptor neurons o Bowman gland: secretes mucus

Olfactory Receptors True bipolar neurons Only neurons to undergo continuous turnover (30-60 days) Arise from basal cells of the olfactory epithelium (stem cells) Apical dendrite consists of ciliated vesicles Unmyelinated axons arise from the basal end if the receptors Only externalized nerve in body Transduction Odorants contact the mucus layer where they bind to olfactory binding proteins (not very specific) The odorant complex interacts with and activates a metabotropic receptor Odorant Specificity Not all olfactory neurons respond to all odorants Olfactory input is derived from the activation of various populations of nerve cells

Human Nasal Cavity: Neurovascular Supply

The two nerves that innervate the nose are the primary olfactory neuron CNI, and trigeminal Olfactory is responsible for the special sensation of olfaction while the trigeminal is responsible for general sensation of pain and temperature

Peripheral Pathway Unmyelinated axons from the receptors form bundles (olfactory filia) collectively known as the olfactory nerve; CN I The filia pass dorsally through the cribiform plate to synapse in the olfactory bulb Olfactory Bulb Organization

Mitral and tufted cells (synapse in the glomerulus, and send information through the lateral olfactory tract; take info away) form primary efferents from the olfactory bulb Centrifugal afferents (send info into the olfactory bulb) from Locus Ceruleus, Raphe nuclei, and Diagonal Band project to the olfactory bulb Consists of 5 layers Granular cells are interneurons and are modulatory

Synpatic Connectivity Periglomerular and granular cells are inhibitory interneurons Mitral, tufted and olfactory neurons are excitatory Centrifugal fibers excite granule cells A lot of sensory integration that takes place right at the level of the glomerulus The lateral olfactory stria is a branch of the lateral olfactory tract and it innervates the amygdala, periamygdaloid cortex, piriform cortex, and entorhinal cortex

Visual System
The Eye an overview Light passes through a variety of media before hitting the retina o (cornea, lens, media filling anterior, posterior & vitreous chamber) Retina is the sensory surface containing the light sensitive cells or photoreceptors Geometry of eye: when looking at an object of interest the retinal image is focused on the fovea o The fovea is a specialized for highest visual acuity Anatomy of the Eye

optic disk: blind spot, optic nerve enters the eye, no photoreceptors lie there; lies in the nasal retina

Functional Terminology Visual field: the visible region of space per eye; what you see Pupillary light reflex: changes in pupil diameter in response to changes in light intensity Accommodation: increasing refractive power by changing the shape of the lens o Closer object -> flatter lens Visual acuity: ability to distinguish two points Visual Fields

Retinal Fields

The image in the retina is flipped by the lens in vertical and horizontal planes Layered Organization of the Retina

Nerve fiber layer contains the optic nerve Within the inner nuclear layer are the bipolar, horizontal, and amacrine cell types that take part in transduction Between the pigmented epithelium and the photoreceptor layer two things occur: o Retinal detachment: a separation if the photoreceptor cell layer from the pigmented epithelium (which is responsible for the acuity of the light energy being transduced into a chemical synapse and if it separates you have blurred vision) o Retinitis pigmentosa: the photoreceptors turnover and are degenerate and normally the debris are removed by phagocytosis but in this condition the debris is not removed and it builds up giving them loss of vision the plexiform layers are where synaptic connections take place and the nuclear layers are where the cell bodies are

Retinal Circuitry

when light comes through the various layers and it activates the rod and cone photoreceptors that sends a signal through the release of transmitter in the outer synaptic layer, that impinges upon the bipolar cells, either a rod or cone bipolar cell, and this occurs in the synaptic layer in the outer synaptic layer rods and cones synapse with the bipolar cells and the bipolar cells synapse with the ganglion cells in the inner synaptic (plexiform) layer; the ganglion cells will then project as the optic nerve out of the eye and back into the brain synapsing in the LGN of the thalamus outer plexiform layer where the energy is transduced into a synapse or into a chemical signal, usually using glutamate as a transmitter the interactions between the bipolar cells and the ganglion cells as triggered by the photoreceptor cells will determine the activity that flows out through the optic nerve into the LGN the horizontal cells and amacrine cells are interneurons that modulate signal transduction

Layer Constituents of Retina

amacrine cells go from one ganglion cell to another

bipolar cells are also being modulated by the amacrine cells inner => closer to lens/vitreous outer => toward pigment epithelium The Retina Light Flow Path o Light flow is from the INner layers toward the OUTer layers o Light passes through different layers of the retina before reaching the photoreceptors

Functional Retina Phototransduction occurs in photoreceptors o Where light energy is transduced into chemical energy (glutamate) Horizontal and amacrine cells mediate lateral effects o Gives greater acuity by keeping out the noise from the signal that impinges upon the rods and cones Bipolar cells process/feed signals forward Ganglion cells = site of action potential generation o Different subtypes of ganglion cells Site where ganglion cell axons exit eye (-> optic nerve) forms the optic disc or blind spot o Blood vessels radiate out of disc to supply the retina

The photoreceptor most common in the fovea is the cone which is responsible for photopic (color) vision; the fovea contains the highest density of cones There is no change in connectivity, just displacement of cell bodies

2 Types of Photoreceptors

Rods highest sensitivity in low light (scotopic) conditions; low acuity; # in peripheral retina >> central retina (where the fovea is and holds all cones) Cones specialized for day (photopic) and color vision; high acuity; concentrated in fovea Phototransduction- takes place in outer segments; which lie within invaginations of pigment epithelium Photopic vision fovea Scotopic vision peripheral > 109

Phototransduction The conversion of light energy (photons) to electrical energy (receptor potental) Phototransduction: 400-700 nm visible spectrum Involves second messenger o Similar to G protein coupled transmission Photopigment for rods is rhodopsin which is max. sensitive for blue green (500 nm) visible spectrum Photopigment for cones is opsin

Final effect of phototransduction is a decrease in Na+ conduction in the photoreceptor cell The closing of Na+ channels results in membrane hyperpolarization

In the retina light energizes or activates the photopigment in the disk membrane which is coupled to a G protein which will activate the effector enzyme which will then inhibit the second messenger and close the ion channel -> loss of sodium conductance Photons are absorbed by photopigment cause a change in photopigments results in G protein coupling inhibition of transmission There are 3 cone opsins: red, green, blue o 1 pigment type per cone

Trichromatic Theory of Vision readout of three cone types object color all types of cones equally active white color blindness missing cone pigment o genes for red and green cone opsins on X chromosome o color vision defects in males > females (1-2% of males) o confusion of shades of red and green Neuronal Mechanism of the Retina post-phototransduction responses in photoreceptor, bipolar cells, and ganglion cells rationale for ON-center and OFF center responses o ON center: increased firing rate with light spot in Receptive field center o OFF center: increased firing rate with dark spot in Receptive field center

In the dark sodium currents are taking place in the rods, which results in a depolarization and a NT release; rod is depolarized in the dark In light there is a hyperpolarization and a decrease in the release of NT; sodium channels are blocked (closed)

Dark vs Light In DARK, there is Na+ based current which is stopped by LIGHT Thus LIGHT decreases the release of NT Main Point: light modulates photoreceptor membrane potential and thus the amount of NT release Response to Glutamate Depends on the Type of (post-synaptic) bipolar cell

In the dark increase release and in the light there is a decreased release which will determine the activity of the bipolar cell, in turn this will determine the activity of the ganglion cell

On and off refers to either releasing a NT postsynaptically or not

Light decreasing glutamate release, the decreased amount of glutamate is inhibiting the ON cells On bipolar cells decreases Na+ channel closure, causes depolarization and you have disinihibition The light depolarizes the ON bipolar cell, the cell is disinhibited by the amount of glutamate and some glutamate receptors that are inhibitory

In the dark you have increased glutamate release that will impinge upon the OFF bipolar cells Increased sodium channel opening depolarization

ON bipolar cell depolarized by light OFF bipolar cell - hyperpolarized by light - depolarized by dark ON & OFF bipolar cells synapse with ON & OFF ganglion cells

Summary Photoreceptor ganglion cell activity o Light results in excitation of ON ganglion cells o Dark results in inhibition of ON ganglion cells o Dark results in excitation of OFF ganglion cells o Light results in inhibition of OFF ganglion cells The Visual Pathways Primarily retino-thalamo(LGN) cortical Some collateral pathways Visual Pathways: Selective Processing Begins in Retina

Parvocellular (X cell) ganglion cell connect to parvocellular in LGB and P cell respond to color stimuli and are photopic ON or OFF center cells

Magnocellular (Y cell) connect to M cells in the LGB and respond to rod input, scotopic

Retinal image

Optic nerve Optic chiasm

Lateral geniculate nucleus Optic radiations

Striate cortex

Info from the ipsilateral and contralateral side will flow into LGB then into striate cortex o Striate cortex = primary visual cortex = V1 = BA 17

Light from the left visual field is represented in the right primary visual cortex Light from the right visual field is represented on the left primary visual cortex Temporal retina does not cross but the nasal hemi retina does cross The right hemi field will fall on the nasal hemi retina and cross So right hemi retina is expressed on the left LGN

Right visual field is located on the left LGN The temporal visual field that projects to the nasal reina crosses in the optic chiasm The LGN & visual cortex receives input from the contralateral visual hemifield

Retinal Projects
Retinal Projections -LGB (LGN) -Sup. Colliculus -Pretectal Nu.
Meye r's Loop

Sup. colliculus Pre te ctal nuc.

Oculom otor nuc. Edinger-Westphal nuc.

Optic radiation

The optic radiations bifurcate, some will extend into the frontal cortex while the others will extend to temporal lobe but all will end up in primary visual cortex The temporal hemifield is ipsilateral while the retinal hemifield crosses There are some collaterals sent to the pretectal nucleus Also collaterals sent to oculomotor nucleus and Edinger-Westphal nucleus: part of the parasympathetic component to the light affects CN III that controls extra ocular eye muscles; this is responsible for PS control of the iris The importance of the superior colliculus is that it is repsonsibe for some visual reflexes The optic tract forms optic radiations and superiorly they form Meyers Loop that extends into the temporal lobe which is important for tumrs in the temporal lobe

Lateral Geniculate Nucleus

The layers represent specific areas of retinal processing Dashed line represents the same locus in hemifield Layers 3-6c are the parvocellular layers o Sustained visual responses o Input from the p ganglion cells Koniocellular layer o In between 6 major layers Layers 1c-2 are magnocellular layers o Phasic visual responses o Input from m ganglion cells There is a separation of phasic visual responses to movement and color response that starts to take place right at the level of the retina and is projected to the LGB in a coded fashion, in the LGb there is an integrative center the information is sent to visual cortex Layers 1,4,6 represent iput from the contralateral side

LGN as a signal processing station

LGN is not just a relay station Information coming in from the retina and going out to the primary visual cortex is actually getting input from other sources within and outside the thalamus Axons from the retina synapse on both the projection neurons that extend to the cortex and interneurons in the LGN. In addition the interneurons receive input from the cortex and from axon collaterals of the projection neurons

Anatomy of Pupuillary Light Reflex

Information from the retina sends some collaterals into the pretectal nucleus then pretecto-oculomotor tract, there is a a bilateral representation of this tract, which pairs along wth motor to CN III and enters into the cilliary ganglion (dilation of the iris)

Visual Field Locations along Geniculo-(LGN)-Cortical pathway

The whole pathway whereby light being represented by the visual pathway will impinge upon the retinal field then to the optic nerve and LGN. From LGN by way of meyers loop, optic radiations to the calcarine cortex represented as striate cortex Superior visual field is represented in the inferior hemi retina then information goes through the optic nerve to the LGN; represented by inferior radiation in Meyers loop and inferior calcarine cortex

Inferior visual field is represented in the superior hemi retina goes through the optic nerve to LGN; optic radiation carries it to the superior calcarine cortex The macula is represented on the fovea which goes into the LGN and through optic radiations to calcarine cortex where you have an upper and lower representations of the macula

Retinotopic Mapping: Visual Field retinal fields neural structure (Primary Visual Cortex)

The upper superior visual field is represented in the inferior calcarine cortex, and the inferior visual field is represented in upper bank of calcarine cortex Macula represents small part of total retinal area but representation on upper bank of calcarine cortex is highest in density

Visual Field Defects Along Geniculo-Cotical Pathway

A: cut through optic nerve blindness in right eye

B: if have a tumor in pituitary region they will grow u and impinge on the optic chaism, patient will not lose peripheral vision (bitemporal hemianopsia) heteronomous because its on opposite temporal fields When you get behind the optic chiasm visual field defects becomes homonymous, same side C: optic tract lesion, homonymous left temporal hemianopsia (cut right optic tract lose left visual field) D: cut meyers loop (from LGB and extend rostrally and dip down into temporal lobe near hippocampal formation then extend to lower bank of calcarine sulcus) - get pie in the sky, left upper visual field E: lesion upper part of calcarine cortex get loss of lower visual field

Information Processing in the Visual Pathway Retinal ganglion cells & visual cells of LGN have concentric, center-surround receptive fields

On center ganglion cells fired with light in the center, with the absence of light they stopped firing in the center but the cells in the surround fired. With diffuse illumination there was no change in firing Off center ganglion cell when light was in middle they stopped firing but the surround would fire; in absence of light in center they would fire while the surround would not fire, diffuse illumination caused no change in firing rate

Information Processing in Striate Cortex (V1) Visual Cortical Columns LGN projects to layer IV of primary visual cortex o Rule of Thumb: all information coming from thalamic nuclei will go to layer IV

Layer IV contains Simple cells o Responds to edges or bars of light o Different than On & Off center Layers I-III & V-VI contain Complex Cells o Responds to light bars with a particular orientation o Form orientation selective columns: will start to fire as bars of light change their orientation Ocular Fominance Columns o Neurons in an adjacent stripe have matching receptive field but responds to stimuli of the other eye o Gives us stereopsis, depth of field

Orientation Selectivity & Orientation Columns in Visual Cortex

Ocular Dominance Columns > Steropsis (depth perception )

Visual Motion Responses Direction selective responses elicited to moving visual images

Important for guiding the eyes in the tracking of moving objects Guiding our hands and arms as we reach out to touch objects Visual motion information processing clearly mandatory in sports

Two Information Processing Streams: Magnocellular & Parvocellular Magnocellular Stream o Begins with M (Y cells) retinal ganglion cells o Project to the magnocellular layers (1&2) of LGN o LGN by way of optic radiations projects to layer IV of primary visual cortex (integrates within the layers of the cortex) o Output from layer VI of striate cortex projects to Association visual cortex (Posterior Temporal & Dorsal Parietal lobes) o Association Cortex responds to movement, orientation & contrast in dim light o Processes information for LOCATING an object in visual space (where stream) o Does not respond to color of an object Parvocellular Stream o Begins with P (X cells) ganglion cells (cone info) o Project to parvocellular layers (3 -6) of LGN o LGN projects to layer IV of primary visual cortex o Layer IV neurons project to two functionally different association neurons through layer VI Respond to shape or orientation (form) Respond to color o Information processed in Inferior Temporal Association Cortex ("What stream)

Hierarchical Organization of Vision Related Cortices

Functional Streams Magnocellular pathway: processes visual motion & some depth information Parvocellular-interblob pathway: processes visual form discrimination and depth Parvocellular-blob pathway: processes color info There is some sharing of function at each hierarchical level. Thus different features of he visual image are processed (extracted) simultaneously in different cortical areas.

Auditory & Vestibular

Auditory System Ear Consists of outer, middle, inner ear OE, ME: conducting apparatus Middle ear contains ossicular chain Inner ear o Fluid filled o Vestibular (balance) o Cochlea (auditory) o Location of sensory transduction Conductive vs. SNHL (sensorineural hearing loss) o Conductive: something that prevents attenuation of sound to inner ear; can be reversed o SNHL: death of the actual hair cells (auditory har cells cannot be regenerated), irreversible

External Ear: external auditory meatus Functional role: o Conducts sounds toward ear drum Resonant frequency: o 3-4kHz o most sensitive hearing Ext ear/head modifies sound from free field o Mechanical processing takes place before gets to the eardrum; mechanical processing begins in the external ear o Sound pressure at entrance differs from eardrum o SPL is frequency dependent Middle Ear Tympanic membrane separates OE/ME Sound induces eardrm to vibrate Sound conduction through ME o Sound transmitted to IE by ossicular chain Air filled cavity 3 ME bones o malleus, incus, stapes o impedance matching: effective transmission of energy from one medium to another; in this case sound energy to fluid in ear 2 ME muscles o tensor tympani (V) o stapedius (VII) o ME reflex

In environment of loud noise these muscles contract and stiffen the ossicular chain so there is very little sound transmission in order to protect the ear Chorda tympani o Branch of CN VII passes through close to the ossicular chain and supplies taste to the anterior 2/3 of the tongue o Can be damaged in ME surgery

Inner Ear

Cochlea ~2 turns Stapes sits on the oval window the entrance to the inner ear In cross section has 3 fluid filled compartments Scala media = cochlear duct; the cochlear duct holds the organ of Corti

Organ of Corti

Consists of: Basilar membrane Tectorial membrane 1 row IHCs, 3 rows of OHCs IHC near modiolus (auditory cell bodies located) OHC near stria vascularis (epithelium layers on lateral wall) Supporting cells Cochlear nerve fibers o Fibers enter organ via osseus spiral lamina Organ of Corti is sensory end-organ for auditory transduction Basilar Membrane motion of the Uncoiled Cochlea

Sound results in piston like action of the stapes against the oval window Induced fluid motion results in a mechanical wave propagating along BM from cochlear base to apex Pressure wave is relieved at the round window

Sound stimulation by a pure tone (single-frequency) induces deflection of BM at a specific distance from stapes o Different frequencies are represented by different parts of the basilar membrane

Auditory Transduction Sound stimulated by pure tone (single frequency) induces deflection of BM at a specific distance Fluid wave moves the organ of Corti Differential displacement of BM/TM results in shear force that mechanically deflects HC stereocilia, leading to auditory transduction Stereocilia deflected lead to K+ channel opening at tips Large K+ influx changes HC membrane potential leading to AP firing in cochlear membrane Cochlear innervation Modiolus o Bony hub o Somas/processes of myelinated bipolar cells SGCs (spiral ganglion cells) innervating different turns 30,000 SGCs per ear SGC fibers to OC via osseous spiral lamina o Peripheral branch Pattern of SGC Innervation of HCs

A large number of the SGCs are dedicating to innervating the IHC OHC are the larger if the hair cell population but only small amount of SGCs are dedicated to innervating them IHC: radial fibers, ~10 fibers/IHC OHC: spiral fibers, 1 fiber to several OHCs

Afferent and Efferent Innervation of HCs

Efferent fibers have their cell body origin in the brain stem in the pontine region they innervate the IHC and OHC in two different ways o If they are inhibitory they block the transmission of sound; so change membrane by hyperpolarizing it and so a higher frequency of sound is required to initiate AP

OHC vs IHC System IHC: Primary afferent system is peripheral pathway important for auditory perception o High resolution pathway created by dense afferent innervation

OHC: Primary afferent system involved with controlling hearing sensitivity o Under direct central (OCB: olivocochlear bundle) control Loud noisy env OCB activated and desensitizes HCs o OHCs shrink in length with OCB stimulation OHCs shrink tightening the ligature between the TM and BM so that theres less shear force to allow propagation of sound o OHCs has a motor rather than sensory function

Tonotopic Organization of the Cochlea

Orderly frequency represented along BM

Ascending Central Auditory Pathway

Cochlear nerve (SGCs) projects to ipsilateral cochlear nucleus o Monaural inputs Cochlear nucleus send fibers to superior olive bilaterally

o SO contains binaural inputs important for sound localizaton o First station where have input from both sides Lateral lemniscus: mainly ascending fibers arising from contra cochlear nucleus & ipsi SO; LL terminates in Inferior colliculus (every point from lateral lemniscus and above there will be input from both ears so any nerve damage at these levels will cause partial loss in both ear) o Trapezoid Body: decussating fibers in ventral pons IC projects to ipsilateral MGB o Via branchium of IC MGB projects to ipsilateral primary auditory cortex o Via sublenticular part of internal capsule Primary auditory cortex (AI) in Heschls gyrus in transverse plane of STG

Speech Centers with reference to Primary Sensory & Motor Cortical Areas

o Speech centers in left hemisphere for most of the population Vestibular System Controls balance Exert strong influence on motor system o Postural control (antigravity muscles) o Eye movements Driven by a constantly active inner ear

2 main components Semicircular ducts are responsive to angular acceleration of the head (head turning) Otolithic organs (saccule, utricle) are responsive to head tilt and linear acceleration Vestibular Labyrinth

Inner ear consists of: o Bony labyrinth (blue) o Membranous labyrinth Perilymph separates bony from from membranous labyrinth Membranous labyrinth (endolymph): o Cochlear duct o Vestibular labyrinth 3 semicircular ducts superior, lateral (horizontal), posterior 2 otolithic organs utricle (horizontal plane) & saccule (vertical plane) o Vestibule of IE: IE entrance where saccule & cochlear base are located

Vestibular Hair Cells Located in Macula and Crista

In the vestibular system the sensory epithelium for transduction is found in discrete places

Vestibular hair Cells: structural and functional polarity

VHCs: sensory receptor celld VHCs separated by supporting cells o Tight junctions between cells seal off endolymph from somas VHC contain multiple stereocilia & a single motile kinocilium o Kinocilium on one side of stereocilium bundle endows VHC with a morphological axis of polarity Axis runs from shortest stereocilium to kinocilium Afferent/efferent fibers synapse on basolateral part of VHC

Utricular Macula

VHCs located in maculae of otolithic organs (utricle & saccule) Stereocilia/kiocilia bindle embedded in otolithic membrane (gelatinous substance) Otolithic membrane contains calcium carbonate crystals (otoliths) o Can break off and go to semicircular ducts and cause benign positional vertigo Otoliths denser than endolymph o Stereocilia/kinocilia deflected with head tilt

Utricle Monitor the Angle of the head Tilt Gravity detectors o Sensitivity to head tilt relative to the horizon o Static detectors dep with increasing head tilt Otolithic organs also monitor linear acceleration o Elevators, cars, etc

Semicircular Duct: Cupula (Membrane) Overlying VHC Stereocilia

Crista ampularis, dynamic labyrtinth for there to be vestibular transduction there must be a movement of fluid Stereocilia/kinocilia bundle of VHCs are embedded in cupula Cupula does not contain otoliths (except in BPV)

Axes of Polarity of VHC Population in One Direction

Axes of polarity of all VNCs in a crista are aligned in same single direction (toward utricle or away from the utricle) Lateral duct : axes toward utricle o + if deflection towards utricle Anterior & posterior duct: axes away from utricle

o + if deflection away from utricle Semicircular Duct: Head Turning Stimulates VHCs When head is turned fluid movement induced by inertia o fluid moves in opposite direction o lateral duct in horizon fluid deflects cupula (trap door) o VHCs stereocilia/kinocilia deflected o Vestibular transduction Note: cupula, OM. & TM pay similar role in sensory transduction in IE Rotatory Head Moton Stimulates Inner Ear Bilaterally

Cristae detect rotary movements of head (angular acceleration) Head turning activates at least one functional pair (both ears) o One ear excited, other ear inhibited o Conjugate eye movements to opposite side o Maintain fixation: preserve gaze o Sense of balance Head turning excites ear turning toward, inhibits ear turning away from

Trigeminal System
Overview Extension of spinal cord dorsal (sensory) and ventral (motor) horns Enters brain stem at mid pons Epicritic for the face o Two point discrimination, fine touch Protopathic for the face o Pain & temperature, itch Conscious & unconscious proprioception for the face Motor for speech and chewing Trigeminal ganglion Ophthalmic Division = V1; sensory Maxillary Division = V2; sensory Mandibular Division= V3; sensory & motor Sensory components of V1, V2, V3 = Portio Major Motor Component of V3 = Portio Minor In this system there is no dermatomal overlap, know exactly which division of CN V contributes to each part of the face Dermatomal Distribution of CN V Ophthalmic V1: Sensory to the Upper Face Forehead Upper eyelid Cornea & conjunctiva Nose (dorsal) & mucus membranes Frontal sinus & anterior dura mater Dermatomal Distribution of CN V Maxillary V2: Sensory to the Mid-Face Upper lip & cheek Nose (lat & post) Temple (ant) Upper jaw (mucous membranes & teeth) Roof of mouth Dura (middle fossa) Dermatomal Distribution of CN V mandibular V3: Sensory to the Lower Face Lower lip & chin Posterior cheek & temple Anterior, external ear Mucus membrane of floor of the mouth, teeth of lower jaw Anterior tympanic & external acoustic meatus

General sensation to anterior 2/3 of the tongue (anterior 2/3 for taste is CN VII) Dura (middle fossa)

V3: Motor to the Muscles of Mastication Masseter Temporalis Med & lateral pterygoids Tensor tympani & veli palatine Importance of Dermatomal Distribution No sensory overlap o Clearly delineate neuropathy All 3 divisions sensory to dura mater o Pain associated with headache Dermatomes Supplied by other Spinal & CNs VII, IX, X o External ear o Afferents travel in spinal tract V & terminate in spinal nucleus C2, C3, C4 o Back of head or neck o Posterior external surface of ear & temple o Anterior neck o Shoulder region Modalities Processed by Nuclei & Tracts of V
EPICRITIC
A FIBERS
DESCENDING (SPINAL) NUCLEUS

MAIN (CHEIF) SENSORY NUCLEUS

In the trigeminal system the A fibers come in, the cell bodies are in the trigeminal (semilunar) ganglion, then project into the brain stem then bifurcate Most epicritic fibers will synapse in the main sensory nucleus of V Some epicritic information will be processed in the descending or spinal nucleus

As the fiber enter midpons it turns caudally and forms a tract, Spinal Tract of V, the first order neuron will synapse in the spinal nucleus of V the second order neuron will exit, turn and cross as the ventral trigeminal thalamic tract (VTTT); crosses in the brain stem

afferent limb comes in from the muscle spindle afferents in the jaw and project to the mesencephalic tract and nucleus of V; the cell body is in the mesencephalic nucleus (in the midbrain) not the trigeminal ganglion then it forms a tract and the tract is part of the efferent limb which exits from the motor nucleus of V (sits next to chief nucleus of V) by way of portio minor to the motor muscle end plate

related to pain and temperature; carried in by A fibers that bifurcate with some going to the chief sensory nucleus and some going to spinal nucleus of V

the information comes in through muscle spindle, joint receptors and pressure receptors; it comes into the brain stem and synapses in the mesencephalic nucleus or the main sensory nucleus of V; then by way of the superior or inferior cerebellar peduncle it goes into the cerebellum

Pathways of Trigeminal Nuclei

CN V enters at mid-pons (1st order) Nuclei extend from midbrain to cervical spinal cord It will bifurcate sending some fibers to motor nucleus of V and some to the chief sensory nucleus of V Some of the fibers will descend as the spinal trigeminal tract and synapse in the spinal (trigeminal nucleus); most of the fibers will cross and form VTTT, after it gets to mid pons some of the fibers from the chief sensory nucleus join the fibers from the spinal tract in VTTT VPM internal capsule VTTT (crossed) 2nd order DTTT (crossed & uncrossed) 2nd order VPM nucluus (thalamus) 3rd order Posterior limb of internal capsule BA 3,1,2 Face

1st order sensory neurons bifurcate upon entry o main sensory n o spinal n 2nd order neurons o VTTT (protopathic) crossed Dorsal to ML o DTTT (epicritic) Crossed & uncrossed Lateral to PAG

Somatotopic Proprioception o Mesencephalic n & tr Lateral to PAG o Mesencephalic tract bifurcates o Sends info to motor nucleus of V on the ipsilateral and contralateral side (jaw jerk)

Specific Functions of Trigeminal Nuclei

As the sensory information coming in for the jaw jerk reflex coming from the sensory component of V3; there is no cell body in the trigeminal ganglion it lies in the mesencephalic nucleus; by way of the mesencephalic tract it will synapse in the motor nucleus of V As it synapses the efferent part of that pathway s by way of portio minor, V3 to the motor end plate of the muscles of mastication Ability to speak is due to the fact that there is cortical control from the corticobulbar tract from the primary motor cortex; this is due to direct and indirect control o Direct from the upper motor neurons to the lower motor neurons or by polysynaptic input (program from broca area for speech is progrmmed in brocas motor speech area and transmitted to primary motor cortex , getting the information for what we ay from the frontal cortex then channeling it down to the motor nucleus of V) For cutaneous reflexes the cell bodies are in the trigeminal ganglion, fibers bifurcate with some going to chief nucleus and the rest to spinal nucleus but they all end up in the motor nucleus of V

Comes in from trigeminal ganglion bifurcates and some of it synapses in main sensory nucleus and some of it descends as spinal tract of V and synapses as spinal nucleus of V The fibers from main sensory nucleus takes several different routes as a 2nd order neuron If its proprioceptive will take DTTT into the VPM of the thalamus If its protopathic it will take the VTTT up through the VPM then posterior limb of the internal capsule to post central gyrus For some cutaneous reflexes goes out to the motor nucleus of V to the muscles of mastication Corneal reflex (blink reflex) is due to the fact that V1 will come in and innervate ipsilaterally and contralaterally the motor nucleus of VII efferent component of VII will go to the eyelid (when air is placed on the cornea the eyes blink) There is a distinction between the blink reflex and the corneal reflex o The corneal reflex is established by V1 through the cornea o the blink reflex occurs by a loud sound or flash of flight through a different pathway

responsible for processing pain free nerve ending come in from V1-V3 and cell body is in the trigeminal ganglion the vast majority of the fibers will come in and descend as the spinal tract of V there are also cutaneous fibers coming in from CN VII, XI, & X that come in and ascend in the spinal tract of V and will also synapse in the descending nucleus of V A: as the information comes in and synapses it will go through the inferior cerebellar peduncle to the cerebellum for proprioception B: the 2nd order neuron synapses in the motor nucleus of V and out to the muscles of mastication C: 2nd order neuron synapses in motor nucleus of VII and the motor output to the facial muscles and blink reflex D: fast pain, VTTT emanating from the decending tract of V into nucleus VPM of the thalamus and into post central gyrus E: slow pain is polysynaptic some information comes from nociceptors that will come in from reticular formation, PAG, and hypothalamus and eventually end up in the intralaminar nuclei and the VPM of the thalamus post central gyrus

Somaototopic Organization of the Trigeminal Nuclei

On the face V1 is dorsal but in the spinal tract it is ventral, V3 was ventral but in the spinal tract its dorsal

There is an organization of not only the tracts but also the types of pain and where they are processed in the nucleus

Trigeminal Neuralgia (Tic Doloreux) Paroxysms of extreme pain More commonly found in V2>>V3>V1 Sudden onset, lasting 1-2 minutes Trigger zones Unknown etiology Treatment: anticonvulsants Corneal Reflex

V1 coming for the cornea surface with a cell body in the trigeminal ganglion Main sensory nucleus and spinal nucleus send an input into the motor nucleus of VII on the ipsilateral side; the output of motor nucleus VII goes to the orbicularis oculi. At the same time it crosses the neuraxis and polysynaptically the main sensory nucleus and spinal nucleus sends input to the motor nucleus of VII on the contralateral side If you cut the motor of VII one side will blink while the other wont

Blink Reflex in Motor Learning Pavlovian eye-blink conditioning as motor learning paradigm Thompson & Kim, 1996 (classical delay conditioning) Study role of cerebellum in conditioning Results show that interpositus nucleus & cerebellar cortex essential locus of plasticity in some forms of motor learning Cerebral cortex not involved Animal given conditioned stimulus last 250 ms and coterminates with air puff to eye (unconditioned stimulus) blink reflex Many pairings of c.s. & u.s. animal has eye blink after c.s. onset and prior to u.s. (once you do it so many times the animal will blink before give unconditioned stimulus)

Tone/light stimulation elicits eye blink Lesion or inactivation of interpositus nucleus results in impaired acquisition of conditioned response but not unconditioned response (reflexive eye blink) Interpositus nucleus essential in this type if motor learning

Motor System I: Reflexes

Muscle Spindle Receptor Specialized receptor capsule (3-4 mm) Oriented in parallel with extrafusal muscle fibers (skeletal muscle) Contains intrafusal muscle fibers o Nuclear bag fibers o Nuclear chain fibers Afferent nerve fibers from two types of endings o Group I primary endings innervate chain & bag fibers o Group II secondary endings innervate chain fibers Sensitive to dynamic & static phases of muscle function o Keeps CNS aware of where muscles are while youre awake Golgi Tendon Organ Slender capsule (1mm long by 100 micrometers diameter) Located in tendons of extrafusal muscle in series with collagen fibers Sensitive to changes in muscle tension o GTO more sensitive to contraction of muscle than it is to stretch Muscle Receptor Organization

No efferents to GTO, GTO only sends signals into the CNS

Muscle Spindle

Highly specialized sensory receptor o 3-4 mm in length o fusiform (spindle) shape o located in belly of skeletal muscle o in parallel o contains intrafusal muscle fibers Intrafusal muscle fibers o Modified striated muscle fibers o Intrafusal fibers = enclosed in fusiform shaped spindle Tension generated on MS o Sufficient to stretch and activate muscle spindle afferents o When stretch send info through Ia afferent cell bodies in the RG, enters in spinal cord and synapse on lower motor neurons, alpha motor neurons which innervate the muscle end plate o When AP is generated from Ia afferent reaches threshold release transmitter which will stimulate efferent and lead to muscle end plate causing the muscle to contract Extrafusal muscle: large muscle mass that generates true force for moving limbs MS is in parallel with extrafusal muscles, endowing MS will role of monitoring muscle length Renshaw cell is important for setting off reflex o When you tap muscle you activate Ia afferent input and alpha motor neuron output o Renshaw cell is an interneuron that shuts this reflex down Gamma motor neuron goes back to the muscle spindle and stimulates the intrafusal muscle fibers All the descending upper motor neurons systems can influence (by interneurons and by directly innervating the alpha motor neurons) the amount of contraction of a muscle which is usually done consciously

Alpha motor neuron goes to the motor endplate of the extrafusal muscle fibers cause muscles to contract and moves whole striated muscle Gamma motor neurons going to the intrafusal muscle will cause the intrafusal muscles to contract

Muscle Spindle Organization

Muscle Receptor Innervation based on myelination = conduction velocities Three classes of neurons o Group Ia afferents from both bag and chain intrafusal muscle types as primary endings o Group II afferents from chain intrafusal muscle fibers as secondary endings flower spray o Gamma motor (fusimotor) efferent neurons (static & dynamic) to intrafusal muscle Group Ib afferents arise only from GTO No efferent innervation to GTO Afferent fibers have soma in a sensory ganglion (DRG) Afferent fibers synapse in dorsal horn (VIII, IX) or in a motor nucleus

Afferent Innervation of Intrafusal Muscle Fibers of MS

Sensory endings o Primary endings = annulospiral

Innervation of Muscle Receptors

Ia fiber coming from bag and chain fibers will innervate laminae IX, alpha motor neuron Ib coming from GTO will always innervate an interneuron, usually an inhibitory interneuron Descending fibers will end on alpha and gamma motor fibers Ib tends to inhibit alpha motor neurons while Ia afferents stimulate it = this creates muscle tone

Golgi Tendon Organ

Slender capsule o 1 mm long x 100 micrometers dia o located in tendon of extrafusal muscle functionally in series with tendon of extrafusal muscle when stretch or contract muscle, you stretch or contract the GTO GTO afferent o Extrafusal muscle contraction induces tension on GTO o Discharge from tension on GTO o So dont tear tendon off the bone too muc tension causes relaxation of muscle GTO location on muscle endows receptor with exquisite sensitivity to small changes in muscle tension

Classification of Afferent fibers on the basis of Fiber Diameter Organizational Principle of Sensory Systems o Different receptor types convey specific information to CNS by way of primary afferents neurons (fibers) of different amounts of myelination o Conduction velocity is related to fiber diameter o Different info is transmitted to the CNS at different speeds Primary sensory afferent o Muscle nerve (proprioceptive afferents) MS and GTO afferents o Cutaneous nerve I-IV correlates to A-C classification o Muscle nerve also LMNs, autonomic, visceromotor A alpha (LMNs), A gamma (fusimotor)

Proprioceptive Afferents: Classification based on fiber diameter

Muscle spindle afferents o Group Ia o Group II GTO afferents o Group Ib Muscle length information is transmitted to the CNS by Ia afferents at a faster rate than muscle tension info by Ib

Summary of Sensory & Motor Innervation of Skeletal Muscle

Alpha MN and gamma MN cell bodies in laminae IX of Rexed in spinal ventral horn

MS vs. GTO: What is the functional difference?

If stretch muscle and record the activity in Ia afferent you have increased afferent firing If stretch muscle and record Ib activity in tendon you have increased firing but not as actively as Ia If stimulate the alpha MN which causes contraction and lifting of the weight the muscle spindle becomes slack and quits firing (and co no longer tell the state of the muscle) If stimulate the alpha MN which causes contraction and GTO starts to fire MS is sensitive to muscle length but without the gamma system it is not responsive to muscle contraction GTO responsive to tension, mostly contraction

Sensitivity to Dynamic & Static Phase of Muscle Stretch Static Gamma MNs o Innervate bag & chain o Endows Ia & II afferents with sensitivity to static phase of muscle stretch (contraction) muscle length Dynamic Gamma MNs o Innervate bag only o Endows Ia afferents with sensitivity to dynamic phase of muscle stretch (contraction) muscle velocity Dynamic Phase of Muscle Stretch: muscle velocity Muscle velocity = rate of change in muscle length Group Ia afferents more sensitive to muscle velocity than length Group II spindle afferents sensitive to muscle length only

Normal Physiological Conditions: Gamma Innervation

With co-stimulation there is firing on the afferent while contraction is taking place so the MS can continue to report Gamma keeps the system responsive to contraction an rates of velocity

Descending Upper Motor Neuron (UMN) Pathways Control Muscle Function

Co-activation of alpha & gamma MNS Normal tonic drive of gamma MNs o Because it keeps the MS responding o Important for normal spinal reflex

Dorsal Root Entry Zone

The more myelinated afferents will enter the dorsal horn more medial 2innervate laminae X, VIII also enter FG, FC The less myelinated afferents will enter the dorsal horn more laterally

General Features of a Reflex Reflex: a stereotypic reaction evoked in response to a stimulus Many of the somatic and autonomic functions mediated by the spinal cord are reflex in nature Reflexes provide: o Valuable clinical tool for assessing the integrity of both the afferent and efferent part of a reflex o General level of excitability of the spinal cord Reflex Arc Consist of 5 Elements Monosynaptic: o 2 neurons afferent and efferent o patellar reflex Polysynaptic: o Reflex center consists of 1 or more interneurons o Flexor withdrawl reflex Stretch (Myotatic) Reflex us mediated by Ia Spindle Afferent

Muscle stretch: o Reflex contraction of homonymous muscle (muscle from which the stimulus is derived) and its synergist (observed) o Relaxation of antagonist muscle Stimulation of inhibitory interneuron via Ia afferent o Called: reciprocal inhibition

Patellar (Knee jerk) Reflex

Stimulus: tap knee o Stretch quadriceps o Ia afferent phasic discharge Reflex: extension at knee o Reflex contraction of homonymous & synergist muscle o Relaxation of antagonist o Reciprocal inhibition (polysynaptic)

Inverse Myotatic Reflex Mediated by Ib (GTO) afferent

GTO afferents exert effects readily observed in extensor muscles

GTO afferents exert effects more widespread in Spinal Cord than more restricted action of Ia afferents (releasing muscle from extension) GTO afferents always stimulate an interneuron either inhibitory or excitatory GTO Ib afferent system is a tension feedback system o High threshold for GTO activation: protective? o Muscle fatigue: decreased muscle tension result of increased tension

Flexor (Withdrawal) Reflex & Cross Extensor Reflex

These reflexes produce responses that serve to protect or escape o Type III & IV afferents from deep receptors in muscle or cutaneous o Afferents convey information about painful or noxious stimuli Stimulate the ipsilateral flexors and inhibit the ipsilateral extensors, alomost simultaneously it will send collateral across spinal cord and stmulate the contralateral extensors and inhibit the contralateral flexors

Flexion at the need to avoid painful stimulus Mediated by multiple spinal levels

Muscle Tone Manifestation of normal or abnormal reflex integration Alpha MN, gamma MN, MS involved in tone Hypotonia decreased resistance to passive limb movement o Flaccid state Hypertonia increased resistance to passive limb movement o Spasticity o Rigidity Muscle Tone: Spasticity Due to UMN lesions o Hyperactive stretch reflexes o Release of inhibitory nature unrestricted reflex arc Clonus sustained series of rhythmic jerks Clasp-Knife effect enhanced resistance then sudden collapse in resistance Muscle Tone: Rigidity Cog-Wheel type of enhanced resistance to passive limb manipulation o Hypertonia not associated with changes in stretch reflexes o Resistance alternately increases and decreases during passive limb rotation Muscle tone is due to stretch reflex: elicited in passive limb manipulation

Muscle tone: manifestation of normal reflex

Supraspinal & Intraspinal Effects on Reflexes Spinal shock o Immediately areflexia (no reflexes) o Reflexes return over time Hyperreflexia

o Hyperreflexia due to Increased sensitivity to cholinergic NTs Loss of descending inhibitory input Collateral spouting Neurological Signs of Upper & Lower Motor Neuron Disease LMN Lesion Signs Muscle Strength o Weakness: individual muscle fasciculations (twitching) Muscle Volume o Marked atrophy Muscle Tone o hypotonia Reflexes o Hyporeflexia o Areflexia o Planter Reflex (N) Manifestation o Flaccid paralysis or paresis UMN Lesion Signs Muscle Strength o Weakness: muscle groups no fasciculations Muscle Volume o Slight atropy Muscle Tone o Hypertonia (spasticity) Reflexes o Hypereflexia o Planter reflex: Babinski sign (extensor) Manifestation o Spastic paralysis

Motor System II: Cortical & Other UMN Systems

Motor Cortical Areas

The motor outflow not only contains our primary and secondary motor cortices but also some sensory feedback information

Motor Cortical Functions M-1 Functions o Execution of simple stereotypic muscle function Amount of force to move limb Speed of movement Secondary Motor Areas o Complex motor movements Goal directed Program

Planning & initiating motor activity Coordinate eye movements Volitional Tracking

Higher Motor Cortical Areas Role of the SMA o A: simple finger movements MI, SI activated o B: complex movements sequence MI/SI + SMA activated (some sort of preparation taking place) o C: mental rehearsal of movement SMA activated only Connections of Cortical Motor Areas Cortical- cortical o Association o Commissural (cross the midline in the corpus callosum; right cortex will interact with the left) Thalamic o Thalamocortical o Corticothalamic S-I o Interaction between primary sensory or secondary sensory into the primary or secondary motor cortex Corticofugal o Corticospinal o Corticobulbar Topographic Motor Maps

Descending Cortical Tracts Overview

LCST & ASCT affects LMNs through alpha and gamma co-activation CBT will extend lenth of midbrain, pons and medulla involve the LMNs of cranial nerve nuclei, pontine nuclei (pontine fibers make up the middle cerebellar peduncle); and red nucleus (give rise to rubrospinal tract in spinal cord)

arise form the cortex LCST 90% cross in the lower medulla as the pyramidal decussation descend in spinal cord in lateral funciculus terminate in laminae VIII, IX (flexor bias) arise from cortex ACST 10% cross at spinal level descend ipsilaterally through anterior funiculus cross then terminate at laminae VIII, IX (flexor bias)

Corticospinal Tracts:

Originate from o Frontal lobe (2/3) BA 4 (1/2) BA 6 (1/2): SMA mainly o Parietal lobe (1/3) Most from somatosensory cortex Frontal CST fibers terminate in ventral spinal gray o Greater innervation density at spinal enlargements & in lateral ventral horn Parietal CST fibers terminate in dorsal spinal gray Lateral CST o Terminates in more lateral parts of spinal cord ventral horn o Control of proximal & mainly distal muscles Ventral CST o Terminates in medial parts of spinal cord o Control of truncal (axial) muscles

Originates from cortex descends through the IC through the base of the midbrain breaks up at pons coalesce again to become pyramids as goes through medulla will cross over as pyramidal decussation descend through lateral funiculus as LCST terminate in laminae VIII, IX

Somatotopic Organization of the Internal Capsule

Corticobulbar Tracts

For motor face area coronal radiata through the genu of the internal capsule bilaterally to upper facial nucleus contralateral to lower facial nucleus Arise form M1 through genu of IC to the medial 1/3 of the crus cerebri as it descends through the midbrain through fascicles in the pons send fibers up into the motor nuclei Analogous to CST, but are UMNs terminating in brainstem Exert influence on cranial nerve motor nuclei Provide volitional control of H/N skeletal muscle CBT travel in close association with CST, except when diverging toward target cranial nerve nuclei CBT projections mainly terminate bilaterally o Facial nucleus clinically important exception Within CN VII there is an upper facial and a lower facial nucleus The upper facial nucleus is bilaterally innervated, ipsilateral and contralateral The lower facial nucleus is contralaterally innervated

UMN vs LMN Facial Weakness

Upper face innervated by both sides where as lower face is representing the contralateral nucleus of VII If cut tract from cortex or anywhere down before it crosses and the patient can wrinkle their forehead but contralateral lower face is paralyzed, drooping of lips, lower face UMN lesion if you cut the tract while its exiting patient cannot wrinkle eyebrow on affected side, ipsilateral the upper face has innervation of both sides so if cut UMN still have lmn to face lower face only has ipsilateral side so affected

MLF joins together CN III, IV, VI o MLF double crossed pathway helps them work together so when LR of the right is contracting moving the eye laterally to right the medial rectus in the left eye is also contracting moving both and the lateral rectus of the left eye is relaxed

Motor System Organization

Two systems driving the spinal cord are the brain stem & cerebral cortex Cerebellum & Basal ganglia which can influence the output of the cortex and brain stem through UMN systems

Hierarchical & Parallel Organization of Motor System

Motor Cortical Areas o Higher motor areas o Planning motor sequence o Frontal, parietal areas o Primary motor cortex (MI): Execution o Modulatory influence Via thalamus o 3 levels of motor control motor cortex cerebellum basal ganglia if one of these get affected will be expressed in the CST, there is no direct pathway from cerebellum, or basal ganglia to the spinal cord so lesions will be expressed through some loss of function from output of UMN systems in CST or CBT o efferent system provides voluntary muscle movement

Descending UMN Brainstem Pathways

Vestibulospinal o posture o balance o two pathways LVST Uncrossed Extensor bias MVST Uncrossed, crossed (mostly uncrossed) Descends through MLF Head and neck movements Rubrospinal o Input from MI o Red nucleus o Crossed, Ventral Tegmental Decussation o Descend through spinal cord, mostly upper spinal cord related to brachial plexus o Flexor bias Pontine (Med) Retiuclospinal Tract o Input from PMC, SMA o Pontine reticular o Uncrossed o Extensor bias Medullary (Lat) Reticulospinal Tract o Input PMC from SMA o Med. Reticular N. o Uncrossed, Crossed o Flexor bias Tectospinal Tract o Input auditory visual somatosensory cortex o Superior colliculus o Crossed Dorsal Tegmental Decussation

o Cervical spinal cord o Head and neck reflexes Review of Spinal Cord Pathways
BRAINSTEM

RETICULOSPINAL TRACTS

TECTOSPINAL TRACT

PONTINE (MEDIAL) RST UX

MEDULLARY (LATERAL) RST UX & x

SUPERIOR COLLICULUS X D. TEG. DEC

ANTERIOR FUNICULUS

LATERAL FUNICULUS

M. ANTERIOR FUNICULUS

EXTENSOR BIAS VIII,IX

FLEXOR BIAS AUTONOMICS VII,VIII,IX

CERVICAL HEAD & NECK VII

Somatotopic Organization: LMN Cell Bodies in Ventral Horn

Decerebrate Rigidity

Cut A: decerebration o Cut below red nucleus o Above vestibular nucleus

o Increase activity of LVST & Pon-RST on Extensors o Extensor Rigidity o Over all extensor tone, no flexion Cut B (Ia): decrease rigidity o Form of gamma rigidity

Cerebellar Effects on Decerebrate Rigidity Stimulate cerebellum (spinocerebellum) o Decrease rigidity o Reduces vestibular nucleus output Cut C = increase rigidity o Disinhibit vestibulospinal output Overdrive extensor tone Cuts A & C then B o No change in rigidity o Alpha MN rigidity Decorticate Rigidity Cut D decorticate posture o Rubrospinal tract is intact Greater input to upper extensors Flexor bias Less input to lower extensor o Upper limbs flexed o Lower limbs extended Decerebrate Rigidity vs. Spasticity Rigidity & spasticity are different types of hypertonia Clinical rigidity is seen in basal ganglia diseases (Parkinson) o Not associated with hyperreflexia Decerebrate rigidity physiologically more closely related to spasticity than clinical rigidity o Decerebrate rigidity & spasticity are associated with hyperreflexia & greater muscle tone The muscles move it but the neurons make it move!

Cerebellum
Function: influence the motor system Evaluating the disparities between intention and action Adjusting motor centers during movements Organization: Extensive sensory input Output mainly to motor nucleus Synaptic transmission is modified Lesion of Cerebellum Do not alter o Sensory thresholds o Muscle strength or movement Impair o Coordination of movement o Reduce muscle tone o Motor learning correct actions and get better with each successive try Gross Anatomy Fissures o Primary Fissure divide ant from post lobe o Posteriolateral fissure separates post lobe from flocculonodular lobe (longitudinal wrapping around brainstem) o Fissures divide the cerebellum into lobes Three lobes o Anterior lobe o Posterior lobe o Flocculonodular lobe Anatomy

4 pains of deep cerebellar nuclei (DCN) o Fastigial Nuclei o Interposed Nuclei Globose nuclei Emboliform nuclei o Dentate Nuclei largest , lateral Most cerebellar afferent fibers send collaterals to DCN Most cerebellar efferent fibers first form synapse with neurons in the DCN

Cerebellar Peduncles Inferior cerebellar peduncle o (Restiform body & juxtarestiform body) o Predominately afferent axons Middle cerebellar peduncle o Branchium pontis o Afferent axons only Superior cerebellar peduncle o Brachium Conjunctivium o Mostly efferent axons (to upper brain centers) Cerebellar Cortex

Lobules and folia o Anterior lobe = 5 lobules o Posterior lobe = 4 lobule o 10th = flocculonodular lobule Outer gray matter (cerebellar cortex) Internal white matter

Three Cell Layers Molecular layer o Stellate cells o Basket cells Purkinje layer Granule cell layer: compact

o Granule cells o Golgi cells Granule cells Only excitatory neurons of the cerebellar cortex Glutamate as neurotransmitter Axons ascend and bifurcate to form parallel fibers, run parallel to the long axis of the folia Purkinje Cells The only efferent neurons of the cerebellar cortex Neurotransmitter: GABA Numerour parallel fibers to one Purkinje cells Input to the Cerebellar Cortex Mossy Fibers o From cerebellar nuclei, spinal cord, brain stem and motor cortex o Forming excitatory synapses (Rosettes cerebellar glomerulus) on dendrites of granule cells and Golgi interneurons Climbing Fibers o From inferior olivary nuclei only o Form excitatory synpases o Terminates in the molecular layer on Purkinje cell dendritic tree o 1:1 ratio purkinje cells to climbing fibers Multilayer Fibers

Synaptic Organization

Mossy fiber will contact granule cell granule cell will send excitatory output to purkinje cells PC also receives input from climbing fiber that so excitatory as well, Stellate, basket cells contribute inhibitory input, golgi cells have indirect inhibitory input through parallel fibers Whatever the PC will decide the cerebellar cortical activity PC control the output of the cerebellar cortex but DCN control the output of the entire cerebellum Purkinje Cells o Receive input from Parallel fibers Climbing fibers o Inhibited by Stellate cells Basket cells Golgi cell DC Neurons o Receive input from: Mossy & climbing fibers inhibited by Purkinje cells

Feedback Inhibition at Cerebellar Glomerulus

Mossy fiber send excitatory input to the granule cell and also send excitatory input into the golgi cell, so excitation of mossy fiber excites golgi cell and granule cell Golgi cell is inhibitory so when activated it works on the granule cell to control it So parallel fiber indirectly modulated by the actions of golgi cell

Feed forward Inhibition at the Molecular Layer

vermis: receive input from the vestibular nuclei, output to medial descending systems intermediate: receives input from spinal and trigeminal systems, output to lateral descending systems lateral: receives input from corticopontine, output to motor and premotor flocculonnodular: input from vest

Principles of Cerebellar Input/Output Input from: o All sensory systems, especially visual and vestibular systems o Brainstem systems Reticular formation Inferior olive Biogenic amine nuclei o Cerebral cortex through pontine nuclei Output to: o Cerebral cortex through deep cerebellar nuclei & thalamus o Brainstem nuclei through deep cerebellar nuclei o Vestibular nuclei Cerebellum from/to spinal cord: uncrossed Cerebellum from/to cerebral cortex: crossed

Vestibulo-cerebellum (Flocculonodular lobe)

Input Ipsilateral vestibular nuclei & ganglion Contalateral accessory olivary nuclei & pons (visual & other sensory input)

Output Direct: vestibular nuclei (efferent) o Does not go through DCN directly through vestibular nuclei Indirect: (via fastigial n.) o Vestibular nuclei (bilaterally) o Reticular formation & accessory olivary nuclei Pathways From vestibular nucleus VST (vestibulospinal tract) & RST (reticulospinal tract) Occulomotor pathways Control, Balance & Eye Movement Lesions will result in o Truncal ataxia (similar to drunkenness) o Wide base stance o Unable to walk in tandem o Nystagmus (arrhythmic oscillation of eye muscles)

Spinocerebellum

(vermal fastigial) Input Somatosensory (trunk) o Via the spinocerebellar tracts Special senses contralateral AON and vestibular nucleus

Output Fastigial nuclei Project to: AON Vestibular nuclei Thalamus-cortex Function: control axial muscle

Intermediate-interpositus Input from: Somatosensory (limbs) Additional sensory (AON, VCT, pons, RCT) Output Interpositus nuclei Project to: Red nucleus Thalamus cortex AON

Function: limb movement via CST and rubrospinal tract Topographic Localization

Spinal Cerebellum Control Motor Execution Lesion will result in: o Cerebellular hypotonia (lower muscle tone & less resistance to passive movement) o Dysmetria (miss target) o Ataxia (poorly coordinated joint motions) o Terminal tremor (oscillates irregularly around target) o Pendular reflexes (limb oscillates as it returns to intial position) Cerebrocerebellum

Input from: Cerebral cortex (pontocerebellar fiber) IO (climbing fiber) Via: Dentate nucleus

Output to: Thalamus-cortex Red nucleus IO Function: planning and control of precise dexterous movements of the extremities Cerebrocerebellum Coordination, movement & motor learning Lesion will result in: o Decomposition of movement o Delayed initiation and termination of motor action Slow in starting movement Rebound or inability to stop movement o Dysdiadochokinesis: inability to perform continuous repetitive movements (flipping hand, tapping finger) o Dysmetria (unable to hit target & intention tremor) Symptoms of Cerebellar Disease Postural instability Delayed initiation and termination motor actions Inability to perform continuous, repetitive movements Errors in smoothness and direction of movement Lack of coordination or synergy of movement Lack of motor spasticity or motor learning

Basal Ganglia
Introduction Motor Activity Modulated by 3 Systems Primary & Secondary Motor Cortex planning & initiation of movement Cerebellum Coordination Basal Ganglia Regulation of Movement Motor System Hierarchy

Motor Cortex Connections Primary & Secondary (Association & Commisural) Corticofugal o Spinal cord (CST) o Brainstem (CBT) o Basal Ganglia (Corticostriate) o Cerebellum (cortico-ponto-cerebellar) Feed forward & feed-back circuits Basal Ganglia Development Four nuclear groups o Caudate o Putamen o Globus Pallidus (externa & interna) Output nucleus from the basal ganglia o Amygdaloid N. Associated nuclei

o Substantia Nigra o Subthalamic Nucleus Components of the Basal Ganglia (Nuclei)

Clinically the Basal Ganglia Refers to 5 Structures 1. Caudate Nucleus Huntingtons Disease 2. Putamen Dystonia 3. Globus Pallidus Carbon Monoxide 4. Subthalamic Nucleus Hemiballismus 5. Substantia Nigra Parkinsons Disease Important role in the execution and termination movement Lesions in any of these structures often causes involuntary movement (dyskinesia)

Huntingtons Disease Causes chorea Autosomal dominant Emotional disorder: apathy, depression Cognitive disturbance: reduced memory, verbal fluency, reasoning Dystonia Definition: repetitive, stereotyped involuntary movements that can be twisting, writhing or jerking but can also be fixed abnormal postures Dystonia is typically caused by lesions in the putamen Like other hyperkinetic movement disorders, there is presumed reduction in Gpi output in dystonia

Focal Dystonia Typically begins in adulthood and involves only one part of the body Usually idiopathic (unknown etiology) Types of focal dystonia o Cervical dystonia (Torticollis) o Blepharospasm (high frequency blinking) Blood Supply to the Basal Ganglia

Connections of the Basal Ganglia Neostriatum

Thalamus sends output to putamen and motor cortex, output from thalamus to cortex is excitatory VA & VL nuclei within thalamus project to cortex

Globus Pallidus

Subthalamus

Substantia Nigra

Direct and Indirect Pathway of Basal Ganglia Key Features Disinhibition primary mode of basal ganglia function Globus Pallidus major output of basal ganglia Subnuclei tonically firing Release inhibitory neurotransmitter Motor Loops: Direct & Indirect Pathways

Cortex will drive the striatum Output from the striatum to the GPi is the direct pathway The striatum influences the Gpe which will drive the subthalamus the subthalmus inputs to the Gpi (gateway to the thalamus)

GPi is the Inhibitory Output Center of the Basal Ganglia There are 3 excitatory pathways (cortex to striatum, subthalamic N to Gpi, thalamus to cortex) the remainder are inhibitory Inhibitory NT is GABA Excitatory NT is glutamate

Direct: Cortex excites the striatum which inhibits the GPi, Gpi is inhibitory to the thalamus so inhibit an inhibitor causing disinhibition of the thalamus which fires glutamate and drives cortex Indirect: Cortex drives the striatum, striatum inhibits the Gpe which is inhibitory to subthalamus, causes subthalamic disinhibition; subthalamus excites Gpi which is inhibitory to thalamus Direct Pathway: Increases Thalamocortical Output

Indirect Pathway: Decreases Thalamocortical Output

Motor Functions through Basal Ganglia Connections

by way of D1 receptor DA will drive direct pathway indirect pathway D2 receptor will inhibit the indirect loop called nigrostriatal modulation

Behavioral Functions through Basal Ganglia Connections

Lesions of Direct & Indirect Basal Ganglia Connections: Hypokinetic Disorders Akinesia o Generated disruption of BG in cortical initiation & generating programmed movements Bradykinesia o Reduction in velocity & amplitude of movement o Lack of disinhibition of thalamus by direct pathway o Increased inhibition of thalamus by indirect pathway Lesion of Basal Ganglia Connections: Parkinsons Disease Bradykinesia Loss of DA neurons in SNpc Degeneration of nigrostriatal pathway Loss of DA input to D1 (+) and D2 (-) receptors Resting tremor, flexed posture

Masked face, shuffling gate Cog wheel/lead pipe rigidity Depression

Partial Lesion of Neostriatum: Hypokinesia

Lesion of Basal Ganglia Connections: Hyperkinetic Disorders (Dyskinesias) Ballismus o Typically hemiballismus o Uncontrolled flinging movements o Lesion in contralateral subthalamic n. Athetosis o Writhing of proximal & distal limbs o Uncontrollable grimacing o Lesion in neostriatum or globus pallidus Tics o Sudden brief action that is preceded by an urge to perform it followed by a sense of relief o Tourettes syndrome (vocal tic) o Motor (involve movements of face or neck) Choreiform Movements o Huntingtons disease o Irregular dance-like movements o Normal muscle strength o Progressive degeneration of neostriatum (caudate) o Autosomal dominant genetic disorder

Lesion of Subthalamic Nucleus

Dopamine Deficiency (PD) leads to overactivity of the Gpi by Decreasing inhibitory influence of direct pathway (accelerator) Increasing excitatory effects of the indirect pathway (break)