Lecture 22 - BIPN140

the detection of pain:

• Specialized nociceptor somatosensory neurons

• Pseudo-unipolar neurons with free nerve endings in skin

• First pain (Aδ fiber), and second pain (unmyelinated C fiber)

ion channels and thermal nociception

• Noxious heat detected by nociceptors expressing transient receptor potential (TRP) channels

• Nonselective cation channels gated by heat and capsaicin

• Nociceptor neurons transmit noxious heat information to spinal cord via action potentials

• Na+ channels in nociceptors are important for pain perception

• Humans with NaV1.7 loss-of-function do not perceive pain

• Humans with NaV1.7 gain-of-function perceive persistent burning pain

nociceptor fiber transmitter release:

• Dual release of glutamate and neuropeptide (Substance P) at the synapse of a C fiber nociceptor axon terminal and a dorsal horn spinal neuron

• Fast excitation by glutamate, slow excitation by neuropeptide

What type of sensory receptor cell will fire Na+ based action potentials

C fiber cell

What type of ions does a TRPV1 receptor pass?

cations

What type of vesicles are found in free nerve ending receptor neurons presynaptic terminals that encode pain sensory information? Choose all that apply

clear core

dense core

the sense of smell:

Orthonasal: smelling with your nose.

Retronasal: flavor perception while eating.

organization of the olfactory system

• Odorants bind to receptors on olfactory receptor neurons (ORNs), in the olfactory epithelium in the inner nose

• Receptors are expressed on ORN cilia

• ORNs project axons through the cribiform plate to release transmitter onto neurons in the olfactory bulb

• the olfactory epithelium (including ORNs), along with its mucus layer, is called the nasal mucosa

• ORNs are bipolar- shaped cells

• single knob-shaped dendrite with olfactory cilia

• single axonal projections to olfactory bulb

what cell type is OR cells?

bipolar

olfactory receptors:

• olfactory are GPCR

• Recognize odor in extracellular domain

• Activate Golf in the intracellular domain

• Variability in protein structure results in sensitivity for different odors

• Human genome has sequences for

~950 olfactory receptors types only

~350 functional versus ~1500 in dogs

• 5 Million Total receptors in Human versus Dogs 300 mil + Cats 200 mil

• Each ORN expresses one receptor

• ORNs expressing the same receptor project to the same glomerulus in the olfactory bulb

odorant receptors (ORs)

• they are GPCRs that signal with cAMP to activate cation channels

• sensory neurons in the nose express a single olfactory receptor gene

olfactory signal transduction

• Golf → activates ACIII → produces cAMP → opens the cAMP-gated cation channel → produces depolarization and calcium influx

• essential molecules for olfactory signal transduction, discovered by gene knockout

what GPCR does this remind you of?

Gs

local circuitry of olfactory bulb

3 key cell types:

• periglomerular cells: inhibits within a glomerulus

• mitral/tufted cells: project to other areas

• granule cells: inter-glomerular inhibition

valence as the primary axis of olfactory

• people are not good at identifying household items by smell

• people tend to describe and group odors by pleasantness

• multidimensional analysis of descriptors applied to odors reveals pleasantness as primary axis

• newborns show signs of innate response to odor pleasantness

• olfactory has a lot of overlap in areas of scent, not clean like other sensory systems

conclusions of olfactory:

• the piriform cortex discards the spatial segregation and chemotopy apparent in earlier stages of the olfactory system

• the piriform shows a highly distributed organization in which different odorants activate unique but dispersed ensembles of cortical neurons

• neurons in the piriform cortex don’t have an apparent continuous receptive fields

organization of the gustatory system:

• Tastants are hydrophilic molecules dissolved in saliva

• Papillae form trenches in the tongue

• Taste buds along the lateral surfaces

• Buds composed of taste cells

• Taste cells clusters around taste pore

• Microvilli (with receptors) extend in the pore

• Taste cells synapse with gustatory afferents

the taste bud:

each contain 3-5 sensory cells

there are about 5000 on the human tongue

taste receptors cells do not have axons;

release ATP on dendrites of cranial nerve fibers

ATP functions as a neurotransmitter binding to postsynaptic ATP receptors

primary taste neurons:

• Apical domain

• Chemical transduction in microvilli inside taste pore

• Salt and sour taste = ionotropic receptors

• Sweet, bitter, and umami taste = GPCRs

• Basal domain

• Electrical signaling and transmitter release

• Voltage-gated and TRP ion channels

• Taste cells release serotonin and ATP to excite afferents

taste transduction mechanisms:

• Five distinct categories of tastants

• Salt Na+ channel

• Sour H+ channel

• Sweet GPCR heterodimer of T1R2 and T1R3

• Umami GPCR heterodimer of T1R1 and T1R3

• Bitter T2R GPCR, acting through G-protein Gustducin

what GPCR type is taste transuduction most similar to?

Gq

what encodes spicy?

TRPV1 spicy is not a “taste” but rather a pain signal caused by capsaicin and other chemical irritants

a labeled-line logic to taste coding

• separate receptors, cells, and pathways for each taste suggests a “labeled line” from peripheral sensation to behavior response

specific taste responses in the cranial nerve are eliminated by knock out of the specific receptor:

• Electrical recording of nerve shows taste responses.

• Knockout of individual taste receptors selectively eliminates specific taste responses.

• This demonstrates the taste cells and their postsynaptic fibers carry information in a labeled line manner.

taste qualities are represented by distinct neurons in the cortex, further indicating what?

labeled line coding

what type of cells project out of the olfactory bulb to other brain areas?

mitral/tufted cells

which sensory cortex does NOT contain a map of its sensory features?

piriform (olfactory)

what is the neurotransmitter released by taste cells?

ATP