9- somatosensory

cheat sheet

vocab
- nerve - bundle of axons
- tract - bundle of axons in CNS
- nucleus - bundle of neurons related to some function
- midline - center of nervous system
  - brain tends to be lateralized - one side is given control
  - ex. speak almost exclusively from left side of brain
information processing
1. feedback (gain)
  - almost always with glutamatergic / GABA
2. feedforward - anticipation
  - estimate things before they happen
  - adjust your behavior in advance of the world (ex. lean before you hit a table)
3. center-surround inhibition (spatial gain)
  - if you touch yourself, brain enhances sensitivity of one point by suppressing information from around it

sensory system overview

we have dorsal root ganglia (DRG) on spinal cord
- axon goes to CNS
- dendrites go everywhere
- pseudounipolar - born polar but become uni-polar
  - dendrite goes straight into axon with cell body off to the side
- do very little processing
dorsal horn - top layer that controls sensory information
in the brain stem, these are called cranial ganglia
- special one is trigeminal ganglia (sensory receptors for face)
oxytocin important clinically
Trp channels - connected mechanically into membrane
dermatomes
- map of sensory parts to brain
- segments of spinal cord correspond to stripes across your body
- brain to feet: cervical, thoracic, lumbar, sacral
shingles - virus where you get stripes of sores - single DRG
- pops out the skin on the dendrite of one DRG
peripheral damage won’t give you stripes of pain
feeling resolution - depends on density of neurons innervating skin
- more neurons - small receptive fields
- two-point discrimination test - poke you at different points and see if you can tell if the points are different
- higher discrimination is better
- discrimination is different that sensitivity (like how it hurts when wounded)

4 neuron classes

they have certain structures that tune them into certain kinds of vibrations
1. Proprioception
  1. muscle spindles - on every neuron - fastest
    - measures stretch on every muscles
    - lets you know where your arm is
  2. Golgi tendon organ
    - measures tension on tendon
    - safety switches - numb your body if you’re over-stressing something (make you let go of hanging on cliff)
2. Ia II - touch neurons
  - superficial - most sensitive
    1. Merkel: hi-res, slow adapt
    2. Meissner: hi-res, fast adapt
  - deeper - sense vibrations, pressure 3. Ruffini: low-res, slow adapt 4. Pacinian: low-res, fast adapt
  - these are in order of depth
  - diabetes - tissue loss and pain / numbness are lost
3. Adelta - fast pain
4. C fibers - pain, temperature, itch
  - very slow, stay on
  - no myelination - Pruritus - newly discovered set of sensory neurons - between pain/touch - itch neurons - new in mice: massage neurons
  - can only fire by stimulating in certain pattern
  - goes to emotion center not knowledge - pleasure
speed proportional to diameter, myelination
adaptation
- some adapt slowly (you keep feeling something)
- some adapt quickly (stop feeling)
  - if you move finger slightly, start firing again when changed
  - better if you feel cockroach that starts moving

pathways

upper-body
- S1 cortex - primary somatic sensory cortex - this is the knowledge of where was touched
- VPL - everything accumulates here in the thalamus then goes to
- Cuneate nucleus - everything goes into this
lower-body (trunk down)
- everything in the lower body goes to Gracile nucleus - in brain stem
special case - sensory for face
- trigeminal ganglion connects into vpm (thalamus) then goes into S1 cortex
proprioceptive pathways
- starts in lower body
  - axons split - half go up to Clark’s nucleus
    - half go back into muscles
  - Clark’s nucleus goes straight into cerebellum
- starts in upper body - goes straight into cerebellum
- thus cerebellum have map of where / how tense muscles are

representation

cortex - this is where understanding is
- dedicates area based on how many neurons coming in
  - lips / hands have more area
- S1 - primary somatosensory cortex
  - most body parts
  - neurons from functionally distinct columns
  - cortex assigns space based on how much info comes in
    - after amputation and time, map grows into lost space
    - map is different when different stimuli are given to fingers
- S2 - secondary somatosensory cortex
  - processes and codes information from S1
  - throat, tongue, teeth, jaw, gum

pathway

mechanosensory
1. DRG
2. Cuneate, Gracile
3. VPL
4. S1
face mechanosensory
1. trigeminal ganglion
2. principal nucleus of trigeminal complex
3. vpm
4. S1
proprioception
- lower body
  1. muscle spindles split
  2. half go to motor neurons
  3. other half go to Clark’s nucleus
  4. clark’s nucleus -> cerebellum
- upper body - straight to the cerebellum

10 - nociception

review

chronic pain is very import clinically
cortex - lets you know if you are sensing something
1. loss-of-function lesion - piece of cortex is lost - lose awareness
  - can come from stroke, migraine-aura
2. gain-of-function lesion = excitatory lesion - like epilepsy
  - cortex comes on when it shouldn’t
  - increased awareness
  - can come from stroke / migraine
“sixth sense” - measuring stretch of all your muscles in cerebellum
nociception = pain
- has nociceptors - neurons that do nociception
- thermoceptors - neurons that sense temperature
two classes of linking receptors
1. Adelta fibers - fast pain
2. C fibers - slow and chronic
Trp channels - mechanically or thermally gated
- let Na+ in
- trpV heat - binds capsaicin
  - in the class of vanilloids
  - birds not capsaicin sensitive
- trpM cold - binds menthol
  - adapts in minutes - stop feeling cold after a while
synapses of nociceptors go to dorsal horn of drg
- nociceptor goes contralateral (must cross midline) - if you cut left side of spinal chord, lose - mechanoception (ipsilateral) from left and nociception (contralateral) from right
- mechanoreceptors, by contrast, send axon up the spinal cord
- dorsal horn has laminal structure (has layers)

know where pain is
- somatosensory cortex
care about pain
- insular cortex - emotional part of brain
  - whether or not you care about pain
  - pairs up with other senses

can have both loss-of-function and gain-of-function lesions in both places
referred pain map - map that refers to a specific problem (ex. esophagus)
visceral pain - don’t know where the pain is
hyperalgesia - increased pain sensitivity
- pain sensing neurons are hyperactive because of inflammation
- pain sensing neuron releases substance P into Mast cell or neutrophil which releases histamine which strengthens receptor
- prostaglandins activate nococeptors
allodynia - when mechanosensation hurts - not understood
turning off pain - add serotonin
1. exercise
2. lack of serotonin ~ mood disorders
  - central sensitization: allodynia
these mechanisms work through introception
- senses chemical imbalances
phantom limbs and phantom pain - if you lose a limb and still feel pain
mechanoreceptors inhibit nociceptors

pathway

nociception
- same as mechanosensory except goes all the way to thalamus
  - doesn’t stop in brainstem
- crosses the midline after first synapse
visceral pain
- axons mainline straight up, go through vpl, go straight to insular cortex

11 - vision (eye)

most of visual system is to read faces
eye
- aqueous humor
- posterior chamber
- lens
- ciliary muscles
- retina
- fovea
- optic disk
- optic nerve and retinal vessels
to see far, stretch lens = accomodation
retina - rods and cones are at back
- cones - color
- retinal ganglion cells sends down signal
12 days to turnover whole photoreceptor disks into PE (pigment epithelium)
- PE is what the rods / cones are in
- PE contains optic disks containing rhodopsin protein that is sensitive to light that break off of rods / cones
light leads to inhibition
melanopsin - receptor for blue light

circuits

accomodation - stretching lens uncrosses lines
function photoreceptor
- usually cGMP is letting in Na/Ca
  - Ca provides negative feedback here
- when light hits, retinal inside rohodopsin activates phosphodiesterase - breaks down cGMP so channel closes and they aren’t let in
light on middle
- depolarizes cone
- excites oncenter
- inhibits offcenter
- these adjust quickly
horizontal cells - takes positive input from photoreceptor and inhibits it back
- inhibits horizontal cells else around it - creates contrast
- have these for each color

pathway

rods / cones (2). horizontal cells - regulate gain control, how fast adapts, contrast adaptation
bipolar cells (4). amacrine cells - processing of movements
retinal ganglion cells
go into thalamus then to cortex (6). small amount go into brain stem and control mood / circadian rhythms

12 - central visual system

cortex is a pizza box
has columns
autophagy - process by which cells eat parts of themselves
- nobel 2016
cones - color
12 day cycle for processing optic disks
photoreceptors have cyclic G-activated channel
- light shuts down photoreceptors
- cell decreases in activity
very roughly - each cone connects to cone bipolar cell
- this gets represented by one column in the cortex
15-30 rods connect to 1 rod bipolar cells
cortex has 6 layers
- each has tons of neurons, mostly pyramidal neurons
- column is a section through the 6 layers - all does about the same thing
- orientation columns responds to specific x,y
  - has subregions that respond to specific orientations
ocular dominance column - both eyes for same coordinate go to same spot
- dominated by one eye
distance
- far cells
- tuned cells
- near cells
V4 in temporal lobe - object recognition

pathways

overall
1. V1
2. V2
3. V4 or MT
central projections
- retinal ganglions
- all go through optic stuff

13 - auditory system

ear parts
- outer
- middle
  - tympanic membrane
- inner
  - cochlea - senses the sound
  - oval window
  - round window - not understood
conductive hearing loss - in the outer/middle ear
sensorineural hearing loss - in the cochlea
- can’t be fixed with hearing aids
humans
- 2-5kHz ~= human speech (can sometimes hear more)
- 30-100x boost for tympanic membrane
  - this differs between people
- 200x focus onto oval window
cochlea
- 4 layers
  - inner hair cells - what you hear with
  - outer hair cells - generate sound
    - generates noise at every frequency except one you want to hear
- otoacoustical emmision - low buzz that is produced
- tenitis - ringing in the ears
  - can be internal
  - can be peripheral - generated by otoacoustical emmision
- high frequencies right next to cochlea
- low frequencies on distal tip
- human high frequency cells die with age
hair cells
- bundle of cilia
- have an orientation
- kinocilium is the tallest
- tall ones are in the back
- dying hair cells - can’t be replaced
  2. loud sounds
  3. certain antibiotics
auditory pathwayz
- MSO - medial superior olive - decides where the sounds is coming from
  - takes input from right / left ear, decides which came in first
- medial geniculate complex of the thalamus
brain shape
- folds are pretty random
- phrenology - shape of skull was based on brain
  - thought it could determine personality
  - false
  - Hsechl’s Gyrus folding pattern is not random
    - argument that if you have one, you are more musical
any sounds is made up of a bunch of frequencies

circuits

K depolarizes hair cells, lets in Ca, releases vesicles

14 - vestibular system

very related to cochlea
- same hair cells
differences
- 1. vestibular system doesn’t use cortex (you don’t think about it)
  - goes right into spinal chord
    1. controls eye movements
  - one of the fastest circuits in the brain
- clinically important
  - you have to be able to have your balance

each column is computational unit of the cortex
ocular dominance column
- one for each eye

labyrinth and its innervation
- semicircular canals
  - can only measure one axis of rotation
  - remember horizontal canal - measures turning head left to right
    - this measures acceleration
    - like a hoola hoop filled with glitter
    - has ampulla at one place in the hoop
    - cupula - sits over the ampulla’s hair cells
    - if the “glitter” hits the cupula, it will bend the hair cells
    - if you keep spinning, fluid starts moving and you stop detecting movement
      - this means the canals adapt mechanically
    - if you stop spinning, fluid keeps moving and system thinks you’re spinning the other way
    - right horizontal canal activated by turn to the right
      - same for left
- scarpa’s ganglion - has hair cells inside
  - sends axons into vestibular nuclei
- lots of fluid (high in K+)
- macula - place where all the hair cells are
  - Ampullae - at base of canals
    - hair cells all in the same direction
  - utricle and saccule - measure head tilt
    - hair cells in multiple orientations
    - these contain otoconia
      - these are little crystals that move with gravity
      - measure acceleration and tilt
tilts do not adapt - they keep firing while you’re leaned back
- they basically report tilt / position at all times
tiplink - connect cilia together for hair cells
- when they move, tiplink move, pull on ion channels
- motor on connected hair cell moves up and down to generate correct amount of tension
  - motor uses myosin and actin
  - harming these proteins can cause deafness
both eyes must always be looking in the same direction
- also must be sitting over image for a while
ipsilateral - same side
contralateral - different side
vestibular ocular reflex VOR - turn your head to the right, eyes move left
- doesn’t require cortex
- only have to learn excitatory

15 - chemical senses

cAMP is used by GPCR