NSCI midterm

topographic map

reflect a point-to-point correspondence between sensory and periphery and neurons within the CNS (e.g. vision in visual field and touch on body surface)

computational map

compare, assess, and integrate multiple stimulus attributes and extract info (e.g. smell and taste)

cortices

sheetlike arrays of nerve cells

commissures

midline crossing axon tracts

gray matter

accumulation of cell bodies

white matter

lipids

substantia

related neurons with less distinct boundaries

locus

a small, well-defined group of cells

ganglion

collection of nerve cell bodies in the peripheral nervous system (basal ganglia is in the CNS, though)

nerve

bundle of axons in PNS (only optic nerve in CNS)

bundle

a collection of axons that run together but do not necessarily have the same origin and destination

leminiscus

a tract that meanders through the brain like a ribbon

genome wide association studies (GWAS)

identify a risk locus

CRISPR-cas9

a unique technology that enables geneticists and medical researchers to edit parts of the genome by removing, adding or altering sections of the DNA sequence

retrograde tracing

tracing the information BACKWARDS - seeing where the information comes from (to cell body)

anterograde tracing

used to identify axons LEAVING a particular region and the terminal buttons of these axons (away from cell body)

CNS has 7 basic parts

spinal cord, medulla, pons, midbrain, cerebellum, diencephalon, cerebrum

brainstem

medulla, pons, midbrain

forebrain

diencephalon and telencephalon (cerebral hemispheres)

cerebrum

receives/sends info to contralateral side of the body

cerebellum

'tiny brain' \-- contains as many neurons as cerebrum, responsible for movement control

external anatomy of spinal cord

- sensory info carried by afferent axons of the spinal nerves enters the cord via the dorsal roots
- motor commands carried by the efferent axons leave the spinal cord via the ventral roots
*once the dorsal and ventral roots join, sensory and motor axons usually travel together in the spinal nerves
CERVICAL, THORACIC, LUMBAR, SACRAL

internal anatomy of spinal cord

- sensory nuclei are lateral, motor nuclei are medial
- dorsal columns: carry ascending sensory info from somatic mechanoreceptors
- lateral columns: include axons that travel from the cerebral cortex to interneurons and motor neurons in the ventral horns
- ventral columns: carry both ascending info about pain and temperature and descending info from brain stem and motor cortex

brainstem anatomy

- sensory nuclei laterally, motor nuclei medially (like spinal cord)
- cranial nerves deal with sensory/motor function of head and neck; regulate levels of consciousness

cerebellum

motor coordination
- contains granule cells and Purkinje cells
- calibrates detailed forms of movement

lateral view of the brain

insular cortex: hidden beneath frontal/temporal lobes
lateral fissure: separates frontal from temporal
pre-central gyrus: locates motor cortex
central sulcus: separates frontal lobe from parietal lobe
post-central gyrus: locates somatosensory cortex

midsaggital surface of brain

- cingulate gyrus: limbic system
- calarine sulcus: locates primary visual cortex

internal anatomy of forebrain

- cerebral cortex: 6 layers (neocortex)
- hippocampal: folded into the temporal lobe and contains 3 layers (archicortex)
- internal capsule: major pathway linking cerebral cortex to brain and spinal cord

thalamus

- cortical relay
- sends info back to brainstem via internal capsule and basal ganglia

meninges

- subarachnoid space contains CSF
- ruptures in the arachnoid membrane are called subdural hematomas

ventricular system

- contain CSF which is produced in choroid plexus
- 500 mL of CSF/day (normal volume of 150 mL)
- CSF flows through ventricles and exits the subarachnoid space by small openings attaching cerebellum and brainstem; there it is absorbed by subarachnoid villi into the blood

transmission of somatosensory info

- cell bodies of afferent nerve fibers are located in ganglia adjacent to spinal cord and brainstem
dorsal root ganglia: body
trigmental ganglia: head

pseudounipolar sensory neurons

cell body found in dorsal root ganglia --\> exits and splits in two
- central branch to dorsal horn of spinal cord
- peripheral branch to spinal nerve, to skin, joint, muscle
also found in sensory ganglia of cranial nerves
- AP's travel past the cell body in the DRG and along central axon to reach synaptic terminals in spinal cords
- because somatic sensory neurons are pseudounipolar, electrical activity does not need to be conducted through cell membrane, but rather continuous peripheral and central axon rate of AP firing is proportional to magnitude of depolarization
RATE OF AP FIRING IS PROPORTIONAL TO MAGNITUDE OF DEPOLARIZATION

pain is sensed by free nerve endings that lack specialized cells

afferents with encapsulated ending have lower thresholds for AP firing so are more sensitive

Piezo

mechanotransduction channels

specialization of somatic sensory afferents

axon diameter: diameter increases, velocity of conduction increases

receptive field: smaller arborization, small RF; more afferents, smaller receptive field

temporal dynamics
- rapidly adapting: onset and may fire at point of termination; info about changes in ongoing stimulation (e.g. movement)
- slowly adapting: constant firing for duration; may convey info about spatial attributes of stimulus (e.g. size, shape)

quality of stimuli (restricted set of stimuli cause certain responses from sensory afferents)
- determined by: channel properties, filter properties

Merkel disks

SLOW ADAPTING
- highly sensitive to light touch (pts, edges, curvatures, form, texture)
- release neuropeptides on the neurites at junctions in a mode similar to synapses
- express Piezo 2

Meissner corpuscles

RAPIDLY ADAPTING
- sensitive to movements of objects across skin (maybe grip)
- skin indentations deform corpuscles to trigger receptor potentials \-- removal of stimulus relaxes corpuscle also generating RP's
- more sensitive than Merkel's because larger receptive field --\> reduced spatial resolution

Pacinian corpuscles

RAPIDLY ADAPTING
- detects vibrations
- 10-15% of mechanoreceptors in hand
- laminar structure filters out all but high frequency
- lower threshold than Meissner's
- may be important in tool use

Ruffini corpuscles

SLOW ADAPTING
- sensitive to cutaneous stretch and digit/limb movements
- 20% of mechanoreceptors in hand
- also found in ligaments/tendons
- long axis of corpuscle lies parallel to stretch
- contribute to sensation of finger position and hand confirmation

mechanoreceptors specialized for proprioception

continuous detailed info about position of the limbs and other body parts in space (muscle spindle, golgi tendon organ, joint receptors)

muscle spindles

- consist of 4-8 specialized intrafusal muscle fibers \-- distributed in parallel arrangements with extrafusal of skeletal
- primary: rapidly adapting responses to changes in muscle length (gp 1a axons), largest myelinated sensory axons
- secondary: sustained responses to constant muscle lengths; transmit info about limb dynamics (gp 2)
-both require Piezo 2

density of spindles varies with function

- muscles generating coarse movement have fewer spindles than those that generate very fine movements
- more precise movement requires more refined sensory input
*artificial stimulation of spindles by vibration produces illusions of altered limb position (only if visual input is prevented)
*proprioception is achieved by integration and visual cues

golgi tendon organs

- low threshold mechanoreceptors in tendons
- sense changes in muscle tension
- formed by branches of Ib afferents
- distributed along collagen fibers that form tendons
- arranged in series with extrafusal muscle fibers

central pathways conveying proprioceptive info

- enters through dorsal horn of spinal cord (however many fibers bifurcate to form both ascending and descending branches and synapse on the dorsal and ventral horn)
- proprioceptive info also reaches cerebellum (movement control)

somatosensory thalamus

- ascending pathways from brainstem and spinal cord converge in ventral posterior complex of the thalamus in a highly organized manner

afferents terminate in a somatopic representation of body and head

- VP lateral: relay from body (via medial lemniscus)
- VP medial: relays from face (via trigemenial lemniscus)

topographic organization of somatosensory info

- medial subdivision: gracile tract
- lateral bundle: cuneate tract

inputs carrying different types of somatosensory info terminate on separate populations of relay cells

info from distinct somatosensory receptor types remains segregated in passage to cortex

primary somatosensory cortex (SI)

- SI located in post-central gyrus of the parietal lobe and has 4 regions
- Brodmann's area: 3a, 3b, 1 and 2 \-- each region contains a complete somatotopic map of body (species specific!)

distinct parallel inputs from VP thalamus

- neurons in 3b and 1: cutaneous stimulation
- neurons in 3a: proprioceptive
- neurons in 2: tactile and proprioceptive

neurons in SI form functionally distinct columns

- e.g. slowly/rapidly responding mechanoreceptors cluster within a single finger
- descending (to thalamus, brainstem, spinal cord) projections outnumber ascending

stereognosis

capacity of the hand to manipulate an object

plasticity in the adult cerebral cortex

- primary somatosensory cortex: responses adapt to differences in stimulation
- lesioning an input: initial lack of response in corresponding cortical area; gradual increase in responding to stimulation of neighboring regions
- changes in cortical representation also induced by less drastic changes in sensory/motor experience (e.g. monkey training, local anesthetic)
- "functional remapping" appears to be a general property of neocortex, observed in visual, auditory, and motor cortices

Y motor receptors

contractile intrafusal fibers are controlled by

touch domes

hair follicle Merkel cell afferents

LEARNING GUIDE of SOMATOSENSORY SYSTEM

- mechanism of signal transduction: same method in all somatic-sensory afferents \-- stimulus changes permeability of cation channels in the afferent nerve endings (generates a 'receptor potential', i.e. depolarizing current)

- anatomical/synaptic pathway to cortex: dorsal column medial lemniscal pathway carries mechanosensory info from the body; trigeminal portion carries information from the face

- mapping rules represented: somatopic mapping further divided into functional columns

head orientation

z axis: yaw
y axis: pitch
z axis: roll

vestibular labyrinth

endolymph

high K+, low Na+

perilymph

low K+, high Na+

vestibular hair cells

- movement of the sterocilia toward the kinocilium (longest hair cell) opens mechanically gated transduction channels located at the tips of the of the stereocilia to depolarize the cell and induce NT release
- movement of the stereocilia away from the koniocilium closes the channels, hyperpolarizing the cell and reducing vestibular nerve activity

otolith organs (utricle and saccule)

saccule: vertically oriented
utricle: horizontally oriented
(striola divides the hair cells into 2 populations with opposite polarities)

when the head tilts, gravity causes the membrane to shift relative to the sensory epithelium

shearing motion between the otolithic membrane and the macular displaces the hair bundles, generating a receptor potential (a similar process occurs with linear accelerations)
- tilting head to one side has opposite effects on corresponding hair cells in the two utricular maculae

how otolith organs sense tilt and acceleration

- tilt --\> sustained displacement
- acceleration --\> transient displacement
- vestibular afferents fire steadily when head is upright; response to tilt is sustained as long as the tilting is sustained

semicircular canals

- ampullae: at the base that houses the sensory epithelium
- cristae: contain hair cells
-cupula: bridges entire width of ampulla and prevents circulation of endolymph

- when head rotates in the plane of the canal, the inertia of the endolymph produces a force across the cupula, distending it away from the direction of movement, displacing hair cells

push-pull of semi circular canals

- all hair cells are organized with their kinocilia in the same direction \-- when cupula moves, the entire population of hair cells is depolarized/repolarized and activity in nerve fibers is increased/decreased
- activity is increased in the pair member on the side toward which the head is moving (decreased on opposite side)

how semicircular sense angular acceleration

- MAX INCREASE in firing: during ACCELERATION
- MAX INHIBITION: during DECELERATION
- during constant velocity, firing rates gradually return to baseline (reflects cupula returning to a non-deflected state)
- sudden deceleration deflects the cupula in the opposite direction, inhibiting firing (firing directly tracking physical position of the cupula)

multisensory, multifunctional, and integrative central vestibular processing

- MULTISENSORY: visual input, premotor neurons, generally sensorimotor
- MULTIFUNCTIONAL: higher-ordering (i.e. spatial orientation, sense of self notion)
- INTEGRATIVE input from: canals/otolith, contralateral vestibular nuclei, cerebellum, visual and somatic sensory systems

Scarpa's ganglion

ganglion of vestibular nerve

distal v. central processes of the vestibular pathway

- distal processes: innervate SCC and otolith organs
- central processes project via cranial nerve to vestibular and directly to cerebellum

vestibular ocular reflex (VOR)

allows for head/eye movement coordination \-- this reflex supports gaze stabilization through eye movement that counters movement of the head
- e.g. head turns left, left horizontal canal excites neurons in in left vestibular nucleus resulting in compensatory eye movements to the right
- vestibular nerve fibers from left SCC project to medial and lateral vestibular nuclei
- excitatory fibers from medial vestibular nuclei cross to contralateral abducens nucleus
- outputs of the abducens nucleus
1. motor pathway that causes the lateral rectus muscle of right eye to contract
2. excitatory projection that crosses the midline to left oculomotor nucleus, where it activates neurons that cause the medial rectus muscle of the left eye to contract

- inhibitory neurons project from the medial vestibular nucleus to the left abducens nucleus

loss of VOR has severe consequences

oscillopsia: 'bouncing vision' \-- inability to fixate visual targets
- unilateral vision can be compensated
- bilateral vision cannot be, as not input from vestibular nuclei

nystagmus

physiological nystagmus: right horizontal canal increases firing, left horizontal canal decreases firing

spontaneous nystagmus: right HC has baseline firing, and the left has no firing at all

caloric testing for nystagmus

in caloric testing for nystagmus, cold water in ear produces nystagmus towards contralateral direction, warm water in ear produces nystagmus towards ipsilateral direction

cold opposite (fast eye movement), warm same (fast eye movement)

because warm, endolymph rises; cold, endolymph falls

vestibular-cervical reflex

a descending protection; medial vestibular nucleus to the upper cervical levels of the spinal cord via the medial longitudinal fasiculus

- mediates head position by reflex activity of neck muscles in response to stimulation of SCC (neck muscle)

(e.g. downward pitch of body, or tripping, activates the superior canals and the head muscles reflexively pull up the head)

vestibulo-spinal reflex

a descending projection; for postural stability (trunk and limb muscles)

- mediated by lateral and medial vestibulo-spinal tracts and reticulo spinal tract

decerebrate rigidity

a result of lesions that cut the brainstem above the vestibular nuclei; rigid extension of the limb
* lesioning the vestibular nuclei relieves this rigidity (this reveals the role of the vestibular system in maintaining muscle tone)

vestibular cerebellar pathways

- cerebellum is a major target of ascending vestibular pathways
- cerebellum is important in integrating/modulating vestibular signals and to enable adaptive change
- differentiating between translational changes
- role of Purkinje cells

vestibular pathways to the thalamus

- lateral and superior vestibular nuclei project to the ventral posterior nuclear complex of the thalamus
- from the thalamus, the vestibular neurons project to cortical areas near the central sulcus

parietoinsular vestibular cortex (PIVC)

important in sense of self motion
- stimulating the PIVC elicits vestibular sensation; this area s activated by vestibular stimulation

vestibular system and visual system

- distinguishing self-generated motion from the movements of objects around us
- vection: perceptual process that elicits the sensation of self-motion when observing motion of an external object

audible spectrum in humans

20 Hz - 20k Hz (15 - 17k Haz for adults)

external ear

pinna, concha, auditory meatus

- auditory meatus selectively boosts sound pressure 30-100x for frequencies around 3k Hz, which is directly related to speech perception

hyperaucusis

painful sensitivity to low sounds

the middle ear

- efficiency of sound transmission in inner ear is regulated by tensor tynpani and stapedius muscles innervated by cranial nerve V

inner ear

- cochlea: transforms sonically generated pressure waves into neural impulses carried by the auditory nerve / also a frequency analyzer
- in response to loud noise, these muscles contract to counteract movement of the ossicles and limit transmission of sound energy

cochlear cross section

- cochlear partition runs from the basal end almost to the apex (the space in between is called the helicotrema)

organ of corti

- hair cells have sterocilia
- inner hair cells receive input from cranial nerve VIII
- outer hair cells receive mostly efferent innervation

basilar membrane of cochlea

high frequencies are heard close to narrow proximal end (towards the base), and low frequencies by distal end at the right (towards the apex) \-- TONOTOPY

mechanoelectrical transduction mediated by hair cells

- inner hair cells are the sensory receptors
- hair cells are epithelial cells that protrude into the scala media
- tip links connect the tups of adjacent stereocilia and translate hair bundle movement into a receptor potential
- movement in the direction of the tallest stereocilia opens the cation selective channel, letting K+ enter, depolarizing the hair cell
- this leads to opening of voltage - gated Ca2+ channels; then neurotransmitter release
* because some channels are open at rest, the receptor potential is biphasic

mechanoelectrical transduction of sound waves

- hair cell RP's follow mechanical displacement of hair bundle
- hair cell can produce a sinusoidal wave in response to low frequency (

HcMET

hair cell mechanoelectrical transduction channel --\> TMC1 (discovered in 2002)

- is a sound/motion activated pore that allows the conversion of sound and head movement into nerve signals

ionic basis of mechanotransduction

- endolymph: high K + ; + 80 mV
- perilymph: low K+, 0 mV
- inner hair cells: -45 mV

endocochlear potential is that the endolymph is 80 mV more positive than the perilymph
- electrical gradient across the membrane of the stereocilia drives K+ into the hair cells; this depolarizes cell which opens K+ and Ca2+ channels in the soma membrane

- hair cells use different external ionic environments to support extremely fast and energy efficient repolarization
* this arrangement ensure the ionic gradient of the hair cell is maintained even during prolonged stimulation
- K + is the source of depolarization and hyperpolarization, allowing maintenance by passive movement alone

cochlear microphonic

the measurable electrical response of the hair cells of the cochlea \-- could be a source of tinnitus (ringing in the ears)

tuning curve

plots minimum sound level required to increase the fiber's firing rate above baseline
(lowest threshold is the characteristic frequency)

characteristic frequency

the frequency to which an auditory nerve fiber will respond t the weakest sound stimulus

label-line coding

changes in the MP of hair cells can code frequencies up to 3kHz, so beyond this...

by the tonotopic organization of the basilar membrane
- the location of the hair cell along the length of the basilar membrane corresponds to the frequency to which it is maximally responsive

phase locking

because hair cells release neurotransmitters only when depolarized, auditory nerve fibers fire only during the positive phases of low frequency sounds
- phase locking is the result: temporal info from two ears to neural centers that compare interaural time differences up to 3kHz)

from the cochlea to the brainstem

- ascending auditory system has parallel organization \-- auditory branch nerve branches to innervate the 3 divisions of the cochlear neucleus
1. aneteroventral
2. posteroventral
3. dorsal
* tonotopic organization of cochlea is maintained in the subdivisions of cochlear nucleus