Unit 2 Flashcards
What is taste for?
- Distinguish between food and poison
- Distinguish between different types of food
- Important for the control of feeding (e.g., GI hormones)
five basic tastes
- Saltiness
- Sourness
- Sweetness
- Bitterness
- Umami
What is the name for a chemical stimuli of taste?
tastant
tastant of saltiness
NaCl
tastant of sourness
proton (H+)
tastant of sweetness
sugar, sucrose
tastant of bitterness
quinine, K+ ion, caffeine
tastant of umami
monosodium glutamate (MSG)
How many taste buds do we have?
2000-5000
basic structure of taste system
each papilla has taste buds, and taste buds have several taste receptor cells that synapse with gustatory axons
taste receptor cells (TRCs)
respond to tastants, about 50-150 in a single taste bud; synapse onto gustatory afferent axons
receptor potential
stimulus-induced change in the membrane potential of a sensory receptor
receptor potential in response to tastants
tastants depolarize taste receptor cells via ion channels (salty, sour) or GPCRs (bitter, sweet, umami), stimulating neurotransmitter release
Can gustatory afferent axons respond to more than one basic taste?
Yes, gustatory afferent axons can respond to more than one basic taste
sensory transduction
the process by which an environmental stimulus causes an electrical response (receptor potential) in a sensory receptor cell
saltiness taste receptor
Na+ channel (ion channel)
sourness taste receptor
H+ channel and K+ channel (ion channels)
sweetness taste receptor
T1R2 + T1R3 (dimer GPCRs)
bitterness taste receptor
T2R; 25 types (dimer GPCRs)
umami taste receptor
T1R1 + T1R3 (dimer GPCRs)
What neurotransmitter is released in response to saltiness?
serotonin
saltiness detection cascade
salty tastant activates special Na+-selective channel in salt-sensitive TRCs, causing Na+ to enter and depolarize the cell, Ca2+ to flow into the presynaptic terminal, and serotonin NT to be released into the synaptic cleft to gustatory axons
What neurotransmitter is released in response to sourness?
serotonin
sourness detection cascade
sour tastant activates H+ channel and blocks K+ channel, causing H+ (and Na+) to enter (and inhibit K+ from leaving) and depolarize the cell, Ca2+ to flow into the presynaptic terminal, and serotonin NT to be released into the synaptic cleft to gustatory axons
bitterness, sweetness, umami detection cascade
tastant activates GPCR, triggering the PLC->IP3->Ca2+ cascade, depolarizing the cell and initiating the release of ATP NT into the synaptic cleft to gustatory axons
What neurotransmitter is released in response to bitterness?
ATP
What neurotransmitter is released in response to umami?
ATP
What neurotransmitter is released in response to sweetness?
ATP
central taste pathway
- Taste receptor cells
- Gustatory nucleus (pathways diverge from here)
- VPM of thalamus
- Gustatory cortex
What is smell for?
warns of harmful substances, combines with taste for identifying foods; detection of pheromones, which communicate reproductive behavior, territorial boundaries, and signal aggression
What is the name for a chemical stimuli of smell?
odorant
anosmia
inability to smell
What is the organ of smell?
olfactory epithelium
olfactory receptor neurons (ORNs)
have GPCR odorant receptors (cAMP) that depolarize in response to activation by odorants; each ORN expresses a single odorant receptor, but can be activated by many odorants
scent detection cascade (olfactory transduction)
- Odorants bind to GPCRs
- Golf subunit activates AC, and cAMP level increases
- cAMP-gated cation channels open, causing an influx of Na+ and Ca2+
- Ca2+-activated Cl- channels open, Cl- leaves cell
- Cell becomes depolarized and fires action potential
What is unique about olfactory transduction and Cl-?
Cl- is more concentrated inside the cell, and when Ca2+-activated Cl- channels open, Cl- leaves the cell, depolarizing it
How many genes encode odorant receptors?
many hundreds of genes encode odorant receptors
How many odorant receptors does each ORN express?
a single odorant receptor is expressed by each ORN (but each ORN can be activated by many odorants due to broad tuning)
broad tuning of ORN
idea that each ORN can detect multiple types of odorants (despite the fact that a single odorant receptor is expressed by each ORN)
olfactory bulb
has ~2000 glomeruli that synapse with ORNs to create a sensory map (each glomeruli receives input from one type of ORN)
combinatorial activation of ORNs
odorants are represented by combinatorial activation of ORNs, meaning multiple ORNs activate in response to a given odorant
glomeruli
~2000 facets of olfactory bulb that synapse with ORNs to create a sensory map; each glomeruli receives input from one type of ORN
sensory map
orderly arrangement of neurons that correlate with certain features of the environment; glomeruli create a sensory map by receiving input from one type of ORN
central olfactory pathway
- Olfactory receptor cells (olfactory epithelium)
- Glumeruli
- 2nd order olfactory neuron (synapses to ORNs on glomeruli)
- Olfactory cortex
unique in that passage through thalamus first is not necessary
complete olfactory transduction cascade
- Odorants bind to GPCR (cAMP) odorant receptors on ORNs in the olfactory epithelium
- Golf subunit activates AC, cAMP levels rise, and cAMP-gated channels open, allowing for an influx of Na+ and Ca2+
- Ca2+-activated Cl- channels open, and Cl- leaves the cell, causing further depolarization and causing an action potential to fire
- Action potentials from the same ORN type propogate to a single glomeruli on the olfactory bulb, where they synapse with 2nd order olfactory neurons
- 2nd order olfactory neurons propogate action potential to olfactory cortex
Technical Tuesday: calcium imaging to visualize neuron activity
GCaMPs are a class of genetically encoded Ca2+ indicators; Ca2+ binds to GCaMP during periods of high neural activity, causing flourescence
olfactory population coding
a large number of neurons specify the properties of a single stimulus; different smells cause activation in different regions of olfactory bulb and olfactory cortex; olfactory system uses temporal coding for population coding
olfactory temporal coding
the olfactory system uses temporal coding, where the timing of spikes caused by different odorants carries information about those odorants
2 categories of memory
- Declarative (explicit) - memory of facts and events
- Nondeclarative (implicit) - memory for skills, habits, and others that don’t have a conscious component
flow of sensory info into long-term memory
memory acquisition
conversion of sensory information into a short-term memory
memory consolidation
conversion of a short-term memory into a long-term memory
Where is memory stored within neural circuits?
distributed memory storage - unique pattern or ratio of activity of neuronal network where memory is distributed and no single neuron represents a specific memory
cellular basis of memory
modification of synaptic strengths forms memory; sensory info “shapes” synapses, forming memories
synaptic plasticity
changes in the strengths of synaptic connections in response to experience and neuronal activity
What biologically strengthens synaptic connections?
- synaptic potentiation (increased efficiency)
- formation of new synapses
What biologically weakens synaptic connections?
- synaptic depression (decreased efficiency)
- elimination of existing synapses
CA3 –> CA1 synapse
synapse in the hippocampus where the CA1 neuron receives input from the CA3 neuron; extremely important for understanding LTP/LDP and overall synaptic plasticity
Long-Term Potentiation (LTP)
a long-lasting increase in the effectiveness of synaptic transmission that is induced by learning (i.e., memory formation); shown by increased EPSP amplitude in CA1
Hebb’s rule
synaptic potentiation (increased efficiency) results when presynaptic activity correlated with strong activation of postsynaptic neuron; i.e., neurons firing synchronously leads to synaptic potentiation
tetanic stimulation
artificial stimulation that can induce LTP or LDP; high frequency stimulation can induce a very strong EPSP, while low frequency stimulation can induce an extremely weak EPSP (below baseline)
What is required for NMDA receptor activation?
Both depolarization AND glutamate needed to activate and allow Ca2+ influx; Mg2+ blocks the channel at certain negative Vm, even if glutamate binds
How does the NMDA receptor act as a co-incidence detector?
Ca2+ entry though NMDA receptor specifically signals that pre- and postsynaptic neurons are active at the same time
How is LTP acheived? (mechanisms of LTP in CA1)
Ca2+ enters postsynaptic terminal through NMDA receptors and activates CaMKII, which acheives LTP by:
1. Increasing effectiveness of existing AMPA receptors via phosphorlyation
2. Upregulating AMPA receptors
BCM theory
synaptic depression (synaptic efficiency) results when presynaptic activity is correlated with a weak depolarization of a postsynaptic neuron; i.e., weak depolarization leads to neurons firing asynchronously which leads to synaptic depression
2 rules of bidirectional plasticity
- Synapses during strong depolarization of postsynaptic neuron causes LTP (Hebb’s rule)
- Synapses during weak depolarization of postsynaptic neuron causes LTD (BCM theory)
How is LTD acheived? (mechanisms of LTD in CA1)
- Increase of protein phosphatase activity
- Dephosphorlyation of AMPA receptors on the membrane
- Removal of existing AMPA receptors
How can Ca2+ trigger both LTP and LTD in CA1?
Ca2+ influx activates CaMKII, which leads to phosphorylation (LTP)
Lack of Ca2+ activates phosphatase, which leads to dephosphorylation (LTD)
What constitutes stable synaptic transmission (memory)?
AMPA receptors are replaced, maintaining the same number; LTP and LTD disrupt this equilibrium
complete early phase LTP cascade
- In the presence of both glutamate and depolarization, NMDA receptors activate, letting glutamate and Ca2+ into the cell
- Ca2+ influx activates CaMKII, which phosphorylates to increase effectiveness of existing AMPA receptors and to insert new AMPA receptors into the membrane (lower amounts of Ca2+ do the opposite in LTD)
Why is phosphorylstion insufficient as long-term memory consolidation mechanism?
- Phosphorylation of a protein is not permanent (memories would be erased
- Protein molecules themselves are not permanent
2 methods of memory consolidation
- Permanently active CaMKII; once activated, autophosphorylation will keep kinases on permanently
- New protein synthesis via cAMP, PKA, and CREB
complete late phase LTP cascade (memory consolidation)
- Ca2+ from early phase stimulates AC to convert ATP to cAMP
- cAMP activates PKA
- PKA phosphorylates CREB
- CREB causes gene expression (new protein synthesis)
CREB-1 vs. CREB-2
CREB-2 is a repressor of gene expression, while CREB-1 is an activator of gene expression (leading to memory consolidation via new protein synthesis)
synaptic remodeling
formation or demolition of synapses during learning and memory
Technical Tuesday: optogenetics
utilization of light and to activate (channelrhodopsins (ChRs)) and inactivate (Halorhodopsin) neurons and control neuron activity
channelrhodopsins (ChRs) (from Technical Tuesday)
subfamily of light-gated cation channels that are activated by blue light to activate neurons
halorhodopsins (from Technical Tuesday)
Cl- pump activated by yellow-light to inactivate neurons (move chlorine ions into the cell, reducing membrane potential)
What are sounds?
sounds are audible variations in the air pressure; basically every object moves the air, creating sound
sound cycle
distance between successive compressed patches of air; peak to peak, trough to trough
sound frequency
number of cycles per second; determines pitch
What is the audible sound range for humans?
20 Hz - 20000 Hz
pitch
high pitch = high frequency
low pitch = low frequency
intensity (amplitude)
defines loudness; high intensity (high amplitude) louder than low intensity (low amplitude)
structural components of the outer ear
- Pinna - funnel/visible
- Auditory canal - entry into ear
structural components of the middle ear
- Ossicles - small bones
structural components of the inner ear
- Cochlea - where sound is converted into signals
tympanic membrane (eardrum)
where sounds are converted into membrane vibration
central auditory pathway
- Sound wave
- Tympanic membrane (eardrum)
- Ossicles
- Oval window
- Fluid in cochlea
- Auditory sensory neuron
What occurs in the middle ear?
pressure through ossicles is amplified, allowing footplate to move like a piston, causing fluid movement in cochlea
auditory receptor cells (hair cells)
receptor cells that are activated by sounds; located on the organ of Corti, which sits on the basilar membrane; have stereocilia (hair-like structure)
2 types of hair cells
- Outer hair cells (OHC)
- Inner hair cells (IHC)
endolymph
liquid in the cochlea that has high [K+] and low [Na+]
perilymph
liquid in the cochlea that has low [K+] and high [Na+]
What happens in the inner ear?
- Oval window in middle ear acts like a piston, causing vibrations in cochlear fluid
- Vibrations in cochlear fluid lead to vibration of the basilar membrane
- When basilar membrane vibrates, stereocilia on hair cells on organ of corti are bent
- Bending of hair cell stereocilia causes sound to be converted into a neural signal (receptor potential)
What causes receptor potential of hair cells?
the bending of stereocilia; when bent in a certain direction, tension in tip link increases, opening the channel and allowing for K+ flow
What occurs at the normal state of tip link in hair cells?
stereocilia are not bent, but K+ channels are partially open, allowing for some K+ flow
hair cell transduction cascade
- Stereocilia bends and tip link is stretched (increased tension)
- Mechanically-gated K+ channels open, and K+ enters the cell
- Hair cells depolarize
- Ca2+ flows into the cell and releases glutamate
What neurotransmitter is released by hair cells?
glutamate
What is unique about hair cell transduction and K+?
K+ flows from outside the cell into the cell, as endolymph has high [K+] concentration
OHC vs. IHC
- Ratio of OHC/IHC is 3:1
- 1 IHC feeds ~10 spiral ganglion cells
- IHCs contribute to 95% of output to spiral ganglion cells
inner hair cells (IHC)
less prevalent than OHC (1:3), but contribute to 95% of output to spiral ganglion cells; a single IHC feeds about 10 spiral ganglion cells
outer hair cells (OHC)
more prevalent than IHC (3:1), but only contribute to 5% of output ot spiral ganglion cells; OHCs amplify basilar membrane deflections (cochlear amplifier) by compression of motor proteins called prestin, which shortens hair cells
prestin
motor protein in OHCs that is compressed in response to OHC depolarization, shortening hair cells and amplifying basilar membrane defelctions; causes stereocilia of IHC to bend more
cochlear amplifier loop mechanism
process of OHCs amplifying basilar membrane deflections, making vibrations more impactful and thereby causing IHCs to bend more
central auditory pathway
- Spiral ganglion
- Ventral cochlear nucleus
- Superior olive
- Inferior colliculus
- MGN
- Auditory cortex
Steps 1-2: input from one ear only
Steps 3-6: input from both ears
What is the most common cause of deafness and how can it be treated?
hair cell damage or loss is the most common cause (auditory nerve often remains intact), cochlear implants common treatment
characteristic frequency
frequency at which a neuron is most responsive
structural properties of basilar membrane base and apex
base is narrow and stiff (high frequency encoding), while the apex is wide and floppy (low frequency encoding)
auditory system tonotopy
the systematic organization within an auditory structure based on sound frequency; represented by:
1. High frequency at basilar membrane base, low frequency at basilar membrane apex
2. There is also a tonotopic map in primary auditory cortex
phase locking
the consistent firing of a cell at the same phase of a sound wave; occurs with sound waves up to ~5 kHz (low frequency)
Can high-frequency sound elicit phase-locked response in neurons?
No, phase locking does not occur with sound waves >5 kHz; sound frequency is encoded by tonotopy at high frequencies
mechanisms for encoding sound frequency
- Low frequency (20-200 Hz) - phase locking
- Intermediate frequency (200-5,000 Hz) - tonotopy + phase locking
- High frequency (5,000-20,000 Hz) - tonotopy
mechanisms for encoding sound intensity
- Firing rate of auditory nerve; more bending of stereocilia, more NT release, more firing
- Number of active neurons in auditory nerve
complete sound detection cascade
- Pinna and ITD/IID localize sound and funnel it into auditory canal
- Tympanic membrane converts sound waves into vibrations
- Ossicles in the middle ear amplify pressure, causing the oval window to fire like a piston
- Cochlear fluid moves the basilar membrane, compressing hair cells on the organ of corti
- OHCs amplify basilar membrane deflections, causing IHC stereocilia to bend more
- Bending of stereocilia causes K+ channels to open, and K+ from the endolymph flows into the cell, depolarizing it
- Ca2+ flows into the presynaptic terminal, releasing glutamate to spiral ganglion cells (95% of this output done by IHCs, which synapse ~10 SGCs)
- Action potential propogates through auditory nerve, then lateral lemniscus to the auditory cortex
How is sound localized in the horizontal plane (duplex theory)?
- Interaural Time Delay (ITD) (low frequency sounds) - difference in time for sound to reach each ear
- Interaural Intensity Difference (IID) (high frequency sounds) - sound at one ear less intense because of head’s sound shadow
Interaural Time Delay (ITD)
the superior olive has binaurual neurons (it receives input from both cochlear nuclei), allowing it to detect the delay between sound reaching the first and second ear; works for frequencies between 20-2,000 Hz
Interaural Intensity Difference (IID)
the head forms a sound shadow, partially blocking sound waves, and using this shadow, the nueron can use intensity to localize sounds; works for frequencies between 2,000-20,000 Hz
How is sound localized in the vertical plane?
the pinna reflects sounds; delays between direct path and reflected path changes as the sound source moves vertically
Do muscles pull or push?
muscles pull, not push; purely contraction
lower motor neurons in spinal cord
muscle contraction is primarily dictated by innervation by lower motor neurons in the spinal cord
neuromuscular junction (NMJ)
chemical synapse between motor neuron axon and muscle fiber
myofibril
composed of stacked sarcomeres; multiple myofibrils form a muscle fiber, and multiple muscle fibers form muscle
What are the thin filaments of the sarcomere?
actin
What are the thick filaments of the sarcomere?
myosin
sliding-filament model of muscle contraction
- Ca2+ binds to troponin, allowing myosin heads to bind to actin
- Myosin heads pivot, causing filaments to slide and muscle to contract
structure of skeletal muscle`
- Muscle is a bundle of muscle fibers
- Muscle fiber is a bundle of myofibrils
- Myofibrils are composed of sarcomeres
- Sarcomeres are composed of actin and myosin filaments
complete muscle contraction cascade (excitation-contraction cycle)
- Action potential causes lower motor neurons in the ventral horn of the spinal cord to release ACh across NMJ
- ACh receptor activates, Na+ enters the cell and causes depolarization (large EPSP)
- Action potential in postsynaptic terminal (muscle) propagates into T tubules
- Sarcoplasmic reticulum releases Ca2+
- Ca2+ binds troponin, allowing myosin to bind actin
- Myosin heads pivot, causing filaments to slide
- EPSPs end, sarcolemma return to resting potential and Ca2+ reuptake occurs by sarcoplasmic reticulum
motor unit
one motor neuron and all the muscle fibers it innervates
How many muscle fibers can one motor neuron innervate?
one motor neuron can innervate multiple muscle fibers
How many motor neurons can innervate a single muscle fiber?
one muscle fiber is innervated by a single motor neuron
3 types of motor units
- Fast fatigable - huge amount of force, but tire quickly and must rest
- Fast fatigue-resistant - sizable force that tires slowly
- Slow - small force that tires very slowly
motor neuron pool
all the alpha motor neurons that innervate a single muscle
What causes sustained muscle contraction?
increased firing rate of alpha motor neurons
2 ways muscle force is controlled
- Firing rate of motor units
- Recruitment of motor units - size principle - small motor units recruited first, allowing for fine activity
Where in the spinal cord are lower motor neurons located?
ventral horn
2 types of lower motor neurons
- Alpha motor neurons - control muscle in an on/off manner; synapse to normal muscle fibers
- Gamma motor neurons - allow for fine-tuning (modulate force generation); synapse to modified muscle fibers (intrafusal fibers)
proprioception
“body sense” which informs us of how our body is positioned and moving in space
muscle spindles
propioreceptors that are innervated by Ia axons to provide sensory feedback to muscle; AKA stretch receptors
stretch reflex
tendency of a muscle to pull back when pulled (e.g., knee-jerk reflex); feedback loops where discharge rate of sensory axons is related to muscle length; monosynaptic
stretch reflex cascade
- Force stretches muscle spindle
- Ia axon rapidly fires action potential to alpha motor neuron, causing muscle to “pull back” (e.g., knee-jerk reflex)
What do gamma motor neurons innervate?
the two poles of intrafusal fibers inside muscle spindle
gamma motor neuron loop
- Gamma motor neuron
- Intrafusal muscle fiber
- Ia afferent axon
- Alpha motor neurons
- Extrafusal muscle fiber
How does the activation of motor neurons affect Ia activity?
- Activation of alpha motor neuron (no/less spindle stretching) -> decrease Ia activity
- Activation of gamma motor neuron (spindle stretching) -> increase Ia activity
“on air” spindles
gamma motor neurons keep spindle “on air”
Golgi tendon
connects muscle to bone and monitors muscle tension via Ib axons; additional proprioceptive input
sensory feedback on muscle tension cascade
- Muscle contracts
- Increased tension of tendon
- Ib axons fire
anatomical arrangement of proprioceptors
- Muscle spindles in parallel with fibers -> muscle length proprioception
- Golgi tendons in series with fibers -> muscle tension proprioception
reciprocal inhibition of flexors and extensors
contraction of one muscle set causes relaxation of antagonist muscle (e.g., bicep/tricep); inhibitory input from interneurons
flexor withdrawal reflex
reflex arc used to withdraw limb from adverse stimulus; poly-synaptic, excitatory input from interneurons that activates flexor muscles on the same side of body
crossed-extensor reflex
activation of extensor muscles and inhibition of flexors on opposite side of body
flexor withdrawal reflex vs. crossed-extensor reflex
flexor withdrawal reflex activates flexor muscles and inhibits extensor muscles on the same leg, while the crossed-extensor reflex activates extensor muscles and inhibits flexor muscles on opposite side
rhythmic activity in a spinal interneuron cycle
- Glu binds NMDA receptor, causing depolarization
- Ca2+-activated K+ channels open, causing K+ to leave and hyperpolarize the membrane
- Glu binds NMDA again, restarting cycle
reciprocal inhibition and rhythmic pattern
Both A and B want to fire but…
1. A fires, inhibiting B
2. A gets “tired” and stops firing
3. B starts to fire, inhibiting A
4. Cycle continues, generating a rhythmic pattern
central pattern generator
circuits that give rise to rhythmic motor activity (e.g., reciprocal inhibition)
What is the largest sensory organ?
skin
What is the stimulus for touch?
pressure on the skin
What receptors detect touch?
mechanoreceptors - convert mechanical force to neural signals
2 types of skin
- Hairy skin - hairy
- Glaborous skin - hairless
What somatic sensory receptor is in the epidermis?
Merkel’s disks
What somatic sensory receptors are in the dermis?
- Pacinian corpuscles
- Ruffini’s endings
- Meissner’s corpuscles
receptive field
the region of a sensory surface that, when stimulated, changes the membrane potential of a neuron
Meissner’s corpuscle
somatic sensory receptor located in the dermis that has:
1. Small receptive field
2. Rapid adaptation (transient response at beginning and end of stimulus)
Pacinian corpuscle
somatic sensory receptor located in the dermis that has:
1. Large receptive field
2. Rapid adaptation (transient response at beginning and end of stimulus)
Merkel’s disk
somatic sensory receptor located in the epidermis that has:
1. Small receptive field
2. Slow, sustained response during stimulus
Ruffini’s ending
somatic sensory receptor located in the dermis that has:
1. Large receptive field
2. Slow, sustained response during stimulus
corpuscle special ending
the corpuscle is a special ending of somatic sensory receptors that allows for rapid adaptation (transient response at beginning and end of stimulus); when removed, adopts slow adaption response profile
larger receptive field vs. smaller receptive field
larger receptive field allows sensory receptor to detect touch at a lower threshold (more sensitive)
two-point discrimination
method used to measure spatial resolution of touch sensation
How do mechanosensitive ion channels open?
- Stretching of lipid membrane
- Pressure on skin causes extracellular protein to “pull” the channel open (from the outside)
- Pressure on skin causes cytoskeleton to “pull” the channel open (from the inside)
Piezo 1 and Piezo 2
mechanosensitive, non-selective ion channels that open via lipid stretching
Technical Tuesday: gene knockout with Cre/LoxP system
Cre: site specific recombinase
LoxP: short sequence recognized by Cre
Cre will cut the DNA section between two LoxP sites in the same orientation, removing a gene
Piezo 2 and Merkel cells
Merkel cells require Piezo 2 to transduce mechanical stimuli into electrical signals
primary afferent axons for pain
Initial pain: Agamma fiber
Second pain: C fiber
primary afferent axons for temperature
C fibers
primary afferent axons for itch
C fibers
primary afferent axons for touch
Abeta
Abeta afferent axons
extremely thick (myelinated), innervate mechanoreceptors on skin for detection of touch
C afferent axons
extremely thin (unmyelinated) and mediate pain, temp, and itch
Where in the spinal cord do primary afferent sensory axons project?
dorsal horn/columns
segmental organization of spinal cord
30 spinal segments across four divisions of spinal cord (cerebral, thoracic, lumbar, sacral)
dermatomes
the area of skin innervated by the right and left dorsal roots of a single spinal segment (one-to-one correspondence between spinal segments and dermatomes)
2 different central touch pathways
- The dorsal column-medial lemniscal pathway - body
- Trigeminal touch pathway - face and top of head
dorsal column-medial lemniscus pathway
touch sensation from body, where one side of the primary somatosensory cortex of the brain is concerned with touch originating from the contralateral (opposite) side of the body
- Dorsal root axon (Aalpha, Abeta, Agamma)
- Dorsal column
- Dorsal column nucleus
- Medial lemniscus
- Thalamus
- Cerebral cortex
trigeminal touch pathway
touch sensation from face, where one side of the primary somatosensory cortex of the brain is concerned with touch originating from the contralateral (opposite) side of the face
somatotopy
the topographic organization of somatic sensory pathway; somatic sensory map that helps determine the location of touch sensation
What is the stimuli for pain?
any stimuli that signal body tissue being damaged or have the potential of causing tissue damage
What are the receptors for pain?
nociceptors - ion channels
3 types of nociceptors
- Mechanical - pressure
- Thermal - temperature
- Chemical - histimines, etc.
most common type of nociceptors
most are polymodal (all 3)
How are nociceptors activated?
- Strong mechanical stimulation, temperature extremes, oxygen deprivation, chemicals
- Substances released by damaged cells - proteases, ATP, K+ ion channels, histamines
What substances are released from damaged cells that activate nociceptors?
- Proteases (-> bradykinin)
- ATP
- K+
- Histamine
TRPV1
thermoreceptor that responds to both hot peppers (capsaicin) and high temperature
Transient Receptor Potential (TRP) channels
cation channels that can be activated by temp, chemicals, light, etc.
TRPM8
thermoreceptor that responds to both menthol and cold temperature
6 distinct TRP channels in thermoreceptors
From coldest to hottest:
1. TRPA1 (cold)
2. TRPM8 (cold)
3. TRPV4
4. TRPV3
5. TRPV1
6. TRPV2
2 major ascending pathways of somatic sensation
- Dorsal column-medial lemniscus pathway
- Spinothalamic pathway
spinothalamic pathway
For pain, temperature, and some touch:
1. Dorsal root axon (Agamma, C)
2. Lateral spinothalamic tract
3. Thalamus
4. Cerebral Cortex
connection between frequency, wavelength, and energy
higher energy = higher frequency = lower wavelength
lower energy = lower frequency = higher wavelength
colors and wavelength
gamma radiation and cool colors have low wavelengths (high energy), while radio waves and warm colors have high wavelengths (low energy)
retina
area where we perceive light
fovea
thinnest area in the retina; visual center that has cones almost exclusively and is very active during the day
What does the cornea do?
the cornea refracts (bends) light towards a single point of the retina
What does the lens of the eye do?
accomodates the cornea by changing shape to provide extra focusing power; allows us to see objects at different distances
2 types of photoreceptors
- Rods
- Cones
both are photoreceptors that convert light into neural signals
Why are rodes and cones arranged in a disc-like manner?
discs provide large membrane surface area for inserting lots of light sensors
rods
photoreceptors that are more senstive to light and are used for night vision
cones
photoreceptors that are less sensitive to light and are used for day vision and color vision
rhodopsin
GPCR light sensor of rods; light causes change in shape of retinal, activating rhodopsin
retinal
used as a cofactor in opsins, it changes shape in response to light
What is the receptor potential of rods?
- In dark, cells are depolarized
- In light, cells hyperpolarize
complete LIGHT detection cascade by rods
- Light causes retinal to change shape, activating rhodopsin
- G subunit activates guanylate cyclase (GC)
- GC converts GTP to cGMP
- Phosphodiesterase (PDE) converts cGMP to GMP
- GMP blocks Na+ channel, causing hyperpolarization
- Release of glutamate is inhibited
complete DARK detection cascade by rods
- Absence of light meand that rhodopsin is inactive
- G subunit activates GC
- GC converts GTP to cGMP
- PDE is inactive, meaning GMP is NOT produced
- cGMP activates cGMP channel, allowing Na+ to flow in and depolarize the cell
- Glutamate is released from the cell
dark current
Na+ ions moving into the cell in dark conditions (absence of PDE), causing depolarization
3 types of cones
- Red (long wavelength)
- Green (medium wavelength)
- Blue (short wavelength)
opsins
GPCR light sensors; in rods, only rhodopsin, but in cones, there are 3 opsins
3 types of opsins in cones
- Red cone opsin (L-opsin)
- Green cone opsin (M-opsin)
3 Blue cone opsin (S-opsin)
Young-Helmholtz trichromacy theory
cones are sensitive to RGB, and when these colors are combined, eyes can tell a difference between million of colors
Why can’t rods detect color?
rods only have a single opsin - rhodopsin - which cannot detect color; this is why we can’t detect color in the dark when rods dominate
scotopic conditions
e.g., nighttime lighting; rods contribute to vision (no color info)
photopic conditions
e.g., daytime lighting; cones contribute to vision
mesopic conditions
e.g., indoor lighting; both rods and cones contribute to vision
dark adaptation
conversion from all-cone daytime vision to all-rod nighttime vision; occurs over minutes to an hour
factors in dark adaptation
- Dilation of pupils (lets more light in)
- Regeneration of unbleached rhodopsin in rods
- Adjustment of functional circuitry
All lead to increased light sensitivty
light adaptation
conversion from all-rod nighttime vision to all-cone daytime vision; occurs over 5-10 minutes
Ca2+ role in light adaptation
to prevent complete hyperpolarization of rods, Ca2+ inhibits conversion of GTP to cGMP, bringing Vm to about -35 mV; allows cones to continue responding to light
laminar organization of the retina
seemingly inside-out layers; light passes through the eye as follows:
1. Ganglion cell layer
2. Inner plexiform layer (synapses)
3. Inner nuclear layer
4. Outer plexiform layer (synapses)
5. Outer nuclear layer
6. Photoreceptors
7. Pigmented epithelium
5 types of cells in the retina
Vertical pathway:
1. Ganglion cells
2. Bipolar cells
3. Photoreceptor cells
Indirect Pathway:
1. Amacrine cells
2. Horizontal cells
What retinal cells fire action potentials and send outputs to the brain?
Only ganglion cells; other retinal neurons produce graded changes in membrane potential
How does information flow in the retina (2 pathways)?
- Vertical pathway
- Indirect pathway
direct (vertical) pathway of info flow in retina
- Photoreceptors
- Bipolar cells
- Retinal ganglion cells
indirect pathway of info flow in retina
retinal processing also influenced by lateral connections
1. Amacrine cells - receive input from bipolar cells and project to ganglion cells, bipolar cells, and other amacrine cells
2. Horizontal cells - receive input from photoreceptors and provide inhibitory feedback signals to other photoreceptors and bipolar cells
amacrine cells
receive input from bipolar cells and project to ganglion cells, bipolar cells, and other amacrine cells; part of indirect pathway
horizontal cells
receive input from photoreceptors and provide inhibitory feedback signals to other photoreceptors and bipolar cells; part of indrect pathway
retinal receptive field
area of retina where light changes neuron’s firing rate
center ON/surround OFF receptive fields of retinal ganglion cells
- Center ON - light only on central photoreceptors increases APs in retinal ganglion cells (firing rate increases in center)
- Surround OFF - light only on surround photoreceptors decreases APs in retinal ganglion cells (firing rate diminished in center)
- Light on both - slight increase in APs, but really weak (close to baseline)
How are receptive fields of RGCs established?
ON and OFF bipolar cells and lateral inhibition from horizontal cells
Excitatory synapse between PR and bipolar cells = center OFF
inhibitory synapse between PR and bipolar cells = center ON
Lateral inhibition via horizontal cells yields opposite response
OFF bipolar cells
have excitatory synapses that preserve the sign of the cone and are therefore hyperpolarized by light (excitatory Glu receptors)
ON bipolar cells
have inhibitory synapses that reverse the sign of the cone and are therefore depolarized by light (inhibitory Glu receptors)
parallel processing in the visual system
simultaneous input from two eyes allows us to compare info in the cortex and also determine depth and distance of an object
How do we gather info about light and dark?
ON-center and OFF-center ganglion cells
central visual pathway
- Photoreceptors in eye
- Other retinal neurons
- LGN
- Visual cortex
retinofugal projection: visual pathways from eye to brain
- Retina
- Optic nerve
- Optic chiasm
- Optic tract
- LGN
- Optic radiation
- Primary visual cortex (V1)
Where does decussation of the visual system occur?
ganglion cell axons from nasal retina cross in optic chiasm
binocular visual field
visual field where we use both eyes to see
What can you see if you’re blind in left eye only?
you can still see some of the left visual field due to overlap
What if you’re blind in the left visual field?
you have optic tract damage and the entire visual field is “broken;” can only see right visual hemifield (right half of normal vision)
What if you’re blind in the peripheral visual fields on both sides?
you have optic chiasm damage and can only see in the binocular visual field
retinotopy
topographic organization of visual pathway in which neighboring cells in the retina send info to neighboring cells in a target brain structure; represented by: position in retina sends info to similar LGN structure to the visual cortex
Can LGN neurons respond to light in more than one eye?
No, they are monocular:
1. LGN layer 2, 3, 5 from ipsilateral (same side) eye
2. LGN layer 1, 4, 6 from contralateral (other side) eye
LGN layer differences
- 2, 3, 5 from same side eye, and 1, 4, 6 from other side eye
- Layers 1 and 2 have larger neurons, while 4-6 have smaller neurons
complete organization of different layers (RGC, LGN, V1)
P-type retinal ganglion (small) —> Layers 3,4,5,6, all Parvocellular LGN neurons (small) —> IVCbeta of striate cortex
- small center-surround receptive fields with sustained response
M-type retinal ganglion (large) —> Layers 1,2, both Magnocellular LGN neurons (large) —> IVCalpha of striate cortex
- large center-surround receptive fields with transient response
Where do most LGN neurons project in the striate cortex
layer 4…
1. Magnocellular LGN project to layer IVCalpha
2. Parvocellular LGN project to layer IVCbeta
3. Koniocellular LGN axons synapse in layers 1/3
some LGN neurons project to layer 2/3
pyramidal cells of striate cortex
have spines and thick apical dendrites; found in layers III, IVC, V, VI
spiny stellate cells of striate cortex
spine-covered dendrites; found in layer IVC
inhibitory neurons of striate cortex
lack spines and form local connections; found in all layers
Technical Tuesday: anterograde tracing
injection of dye to trace from soma to synapse
Technical Tuesday: retrograde tracing
injection of dye to trace from synapse to soma
ocular dominance columns
stripes of neurons in the visual cortex of certain mammals (including humans) that respond preferentially to input from one eye or the other; found in layers > IV (IVC, VI, etc.)
Where are binocular neurons found?
most layer III neurons are binocular (but not layer IV or greater)
receptive fields of the striate cortex
monocular receptive fields: found in layer IVC; have one receptive field
binocular receptive fields: found in layers before IVC (mainly III); have two receptive fields
patterns of intracortical connections within striate cortex
some cortical neurons project locally to deeper or shallower layer, establishing “columns” of interacting neurons, but others project sideways (horizontally)
orientation selectivity of neurons in striate cortex
neuron fires action potentials depending on the orientation of the bar of light in visual field, which is important for the analysis of object shape
orientation-selective columns
adjacent cortical neurons tend to have similar orientation selectivity, and neighboring cortical cells share identical or similar orientation selectivities (pinwheels)
direction selectivity of neurons in striate cortex
neuron fires action potentials in direction-dependent response to moving bar of light; important for the analysis of object motion
How are receptive fields of cortical cells unique?
they are usually oblong instead of circular, making cortical cells orientation-selective - respond best to light with specific orientation
How are oblong cortical center-surround fields formed?
input from several LGN neurons with adjacent circular fields combined
cytochrome oxidase blobs
monocular, no direction-selectivity, likely orientation selectivity, but specialized for the analysis of object color
What info does the magnocellular pathway process?
motion
What info does the blob pathway process?
color
What info does the parvocellular pathway process?
shape
What is the capability of a cortical module of the striate cortex?
each module is capable of analyzing every aspect of a portion of the visual field (direction, color, orientation, light/dark, etc.)
