Exam 4: Chemical senses Flashcards
what is the general structure of the olfactory system prior to the olfactory bulb?
- receptor cells are at the roof of the nose
- they sit on the olfactory epithelium and have receptors that detect airborne odorants
- these efferent converge into the olfactory nerve and then release NT on the olfactory bulb
- they pass through the cribriform plate to the olfactory bulb
T/F olfactory receptor neurons fire action potentials?
True
- different from auditory and vestibular
when there is a head force trauma, what’s the easiest place to get a fracture?
at the cribriform plate which cuts the olfactory receptor neuron axons
T/F the olfactory receptor neurons cannot regenerate?
False
- The receptor cells can regenerate and reform synaptic connections in the olfactory bulb
T/F olfactory receptor neurons are hair cells? What do they have at their ends sensing odorants?
True
- they have olfactory cilia
- the sensor is at the cilia and not elsewhere on the hair cell
Bowman’s gland
releases the mucus that keeps the nasal cavity moist
how did scientists do testing for the trigger of olfactory hair cells?
they released odorants with a pipette and used an electrode to record the cell body
- when they got inward currents via a voltage clamp then they could tell that’s what triggered the hair cell
- the hair cell only responds when odorants are released at the cilia
how do dogs differ compared to humans in olfactory detection?
dogs have superior olfactory systems
- they can detect a few parts per trillion (not billion) vs humans
how many ORNs (hair cells) do dogs have compared to humans?
1 billion compared to 12 million in humans
what can dogs be trained to detect odors from? What might they be able to detect?
atypical odors from human breath, sweat, urine and skin; Diabetes, cancer, fear, etc.
- Diabetic sweat has higher concentration of glucose and urea compared to normal
T/F humans olfactory bulb is smaller than other mammals?
True
- rats have a relatively larger olfactory bulb for their body size compared to humans
where is the olfactory circuit?
the entire circuit is at the base of the brain ⇒ doesn’t go through the thalamus
all vertebrates have _____ but only mammals have a ______?
olfactory bulb; neocortex
what is the general track for olfaction?
- olfactory receptors
- cranial nerve 1
- olfactory bulb
- olfactory tract
- pyriform cortex, olfactory tubercle, amygdala, and entorhinal cortex
- pyriform goes to orbitofrontal; all 4 go to orbitofrontal, thalamus, and hypothalamus; entorhinal goes to hippocampal formation
what is special about the olfactory tract from other sensory systems?
it bypasses the thalamus when it goest to the orbitofrontal cortex
what is special about the entorhinal cortex?
smell through this pathway triggers memories
what is the cellular circuit for olfactory signaling? (ORNs to “brain”) (4)
- New olfactory receptor cells/neurons (ORNs) can be generated from surrounding cells in the olfactory epithelium
- Olfactory nerve (CN1)
- Axons from 25,000 different ORNs can project to one glomerulus
- Axons for mitral and tufted cells form the olfactory tract that projects to the brain
what is the bottom to top cell layering (what cells?) in the olfactory system?
ORNs => axons => glomerulus => tufted and mitral cells => granule cells => olfactory tract => olfactory cortex
how does top down modulation work in the olfactory system?
Granule cells receive top down modulatory signals from the piriform and entorhinal cortices ⇒ group of interneurons doing the modulation possibly
where is olfactory modulation generated from?
the subventricular zone (SVZ) of the brain
T/F are there neuronal cell bodies in a glomerulus?
False
- there are no neuronal cell bodies in an olfactory glomerulus
- the glomerulus is a synaptic processing unit composed of axons
what projections are the glomerulus synaptic processing composed of?
ORNs axons, dendrites from mitral, tufted cells, and periglomeruluar interneurons
T/F do granule cells undergo adult neurogenesis?
True
- as many as 1% of granule cells get replaced per day
what are the stages of neurogenesis for granule cells?
- proliferation SVZ
- fate specification as neuroblasts
- migration: tangential/radial
- synaptic integration as new granule neurons
what happens when odor stimulations go from low to high concentrations? Indole ex?
there are distortions at a high concentration
- low concentrations of indole gives you a floral sense but in high concentrations its unpleasant which shows up on the brain different places
how do subtle molecular changes produce different smells in D-carvone vs L-carvone (enantiomers)
spearmint vs caraway odors
- caraway smells musky
T/F there is a single molecular structure that encodes a specific odor?
False
- natural odors have multiple chemical compounds
what is good vs bad smell?
may depend on the odorant concentration as very similar molecules (odorants) can be perceived very differently
T/F different regions of the brain may be involved in perception of different types of smell such as unpleasant vs pleasant?
True
T/F the ability to distinguish odorants doesn’t change with age?
False
- ability to distinguish odorants decline with age
what does loss of olfaction suggest regarding neurodegenerative diseases?
early Parkinson’s, Alzheimer’s, dementia
- schizophrenia is associated with olfactory hallucinations
what may cause neurodegenerative diseases?
May be due to reduced adult neurogenesis
how many different odorants can humans distinguish?
10,000
T/F each receptor responds to one odorant?
False
- Each receptor responds to multiple odorants
T/F a single odorant can activate multiple receptors?
True
T/F there are 10,000 different receptors?
False
- there are not
how do olfactory responses compare to audition? visual responses?
slower than both
how do odorants bind with receptors?
different parts of the odorant receptors can bind to different parts of the odorant
- which is how you develop combinations of binding to receptors
- neurons may respond broadly or preferentially to multiple odorants
is the odorant channel ion mediated or stretch mediated?
No, it cannot be either to bind to multiple different odorants
what is the structure of the odorant receptor?
7 TM domains and G protein coupled receptor
are the inside and outside regions of the odorant receptor similar to other GPCRs?
- Intracellular region is just like other GPCRs
- Extracellular region specific to odorants ⇒ little homology to other GPCRs
how many receptor types does an ORN express? How many types are there total?
only 1 ; 400 types of odorant receptors total based unique extracellular domains
how many total numbers of ORNs (not types) do humans have?
10-20 million
how does the odorant GPCR pathway work?
- the odorant binds to the GPCR externally
- the active portion of the G protein (Golf) breaks off and activates adenylyl cyclase (3)
- this produces cAMP from ATP
- the cAMP activates Na+ and Ca2+ cAMP gated channel (cyclic nucleotide gates channel aka gCNG) to let in Ca2+ and Na+ => some K+ comes in too
- the Ca2+ goes and opens a different gated channel that lets out Cl- and also activates a Na+/Ca2+ exchanger so Ca2+ goes out and Na+ goes in
when odorants bind the GPCR does this lead to depolarization or hyperpolarization? via what?
depolarization; cyclic nucleotide and Ca2+ gated channels
what is unusual about depolarization of odorants cells?
unusually high concentration of ciliary chloride, and its exit accounts for 50-85% of the depolarization
- only in the cilia of the hair cell there is a reverse concentration gradient for chloride where it is high inside and low outside
what generates the steady state level of high chloride in the cell?
a pump called NKCC1
- Intracellular Cl- is kept elevated above electrochemical equilibrium by the Na+/K+/2Cl- co-transporter NKCC1
- lets in 1 Na+ and K+ and 2 Cl-
- uses the Na+ and K+ gradients to pull Cl- along with it
what does negative ions leaving the cell lead to?
depolarization
- this is not typical for cortical neurons ⇒ specialized for odor cells
where does olfactory transduction take place?
in the cilia of the olfactory receptor neuron
- gCNG allows Na+ and Ca2+ to enter the cilium
- elevation in Ca2+ concentration activates a Ca2+ activated Cl- channel allowing efflux of Cl-
where is Cl- concentration high? where is it low?
chloride concentration is high in the cilia but low in the cell body due to the NKCCI pump
when is odor identification the highest between 20-70?
20 and linearly decreases
what is the full pathway for taste signaling?
- afferents on the tongue and back of the throat all innervate the brainstem at the medulla at the nucleus of the solitary tract
- this goes to the VPM as ell as the hypothalamus and amygdala
- the VPM goes to the insular and frontal taste cortices
- these to go to the amygdala
T/F there are be multiple taste cell receptors in one taste bud?
True
papillae
Bumps on the tongue that each have many taste buds
- the papillae sticks upward and there are trenches around all of them that contain the taste bud on the sides (like a canyon with rocks jutting out of the sides as you look down to the bottom)
taste bud
group of taste cells organized around a taste pore which connects to the gustatory afferent axons
T/F taste bud taste cells undergo action potentials initiated in the taste receptors?
False
- There is no action potentials initiated in the taste receptors
T/F every kind of receptor is expressed all over the tongue and there is no general distribution?
False
- every kind of receptor is expressed all over the tongue but there is a general distribution
nM sensitivity; mM sensitivity
Concentration sensitivity that small amounts of bitter (nM compounds) can detect; concentration sensitivity that salty and sweet/umami cells detect via L-glutamate, GMP, etc.
where are the circumvallate papillae?
at the back of the tongue going from the left to right side
- CN IX
where are the folate papilla located?
at the back on the tongue on the ventral lateral sides
- not on top of the tongue
where are the fungiform papillae?
at the front o the tongue mostly around the lateral edges and less medial
- CN VII
what ligand gated ion channels do taste stimuli activate?
Can directly and indirectly modulate Na+, K+, Ca2+ and other cation channels
what GPCR’s do taste stimuli activate?
GPCRs that modulate PLC, PDE, and AC signaling
which taste stimuli activate ion channels?
- salt
- sour/acids
which taste stimuli activate GPCRs?
- sweet
- bitter
- umami/amino acids
what is the pathway of salt and sour (acid) stimuli?
- activate and open an ion channel
- activate Na+ channels so Na+ comes in, activate K+ channels so K+ goes out, and activate Ca2+ channels so Ca2+ comes in leading to depolarization
- Ca2+ internal reserves are also opened in the ER and these allow for NT release to a primary sensory neuron
- primary sensory neuron has an action potential
what is the pathway of sweet, bitter, and umami stimuli?
- activation of a GPCR
- activation of PLCB2 second messengers that open Na+, K+, and Ca2+ channel and activation of Ca2+ ER reserve and TRPM5 channels that let in more Na+
- the Ca2+ allows for NT vesicle release to primary sensory neurons
- primary sensory neuron that fires action potentials
what neurotransmitters are activated from taste stimuli? Which is the major vs minor?
serotonin and ATP; ATP is major
what happens if you knockout P2X2 and P2X3
they are ATP receptors on the sensory nerve fibers which totally eliminates transmission of the signal from the taste receptor cells to nerve fibers
- ATP is required for taste sensation
what happens with the knockout of 5-H3T receptors?
they are serotonin receptors that may regulate the taste sensation but are not required for taste
Gustudic
the G-protein for sweet, bitter, and umami/savory flavors
what does activation of PLCB2 lead to?
synthesis of IP3 and activation of IP3R3 receptors which releases intracellular calcium from the ER
- this opens TRPM5 which causes Na+ influx to depolarize the cell
what type of (T) GPCR do sweet molecules activate?
T1R2 and T1R3 heterodimer GPCR
what type of (T) GPCR do bitter molecules activate?
T2R monoprotein
what type of (T) GPCR do umami/savory molecules activate?
T1R1 and T1R3 heterodimer GPCR
what types of detection to TRP channels have?
- chemical/taste
- thermodetection
TRPM8
cool and minty channel activated by menthal
- menthal is a natural compound in mint plants ⇒ fools the brain into thinking that skin and throat have been cooled
- We can knock out the cool vs minty receptors to get different reactions from the brain
TRPV1
transient receptor potential V1 found on the tongue and the skin
- Capsaicin activates the VR1 receptors (by passing through the lipid bilayer to bind inside), as do heat and acids
- Administration of capsaicin results in desensitization of the receptor on the pain fiber, leading to deactivation of the receptor => opening V1 lets in Ca2+ and Na+
- Capsaicin is used in heat rub pain relief remedies
End card
:)
