Key takeaways U2 Flashcards
What is one challenge for both taste and smell neurons
how to maintain the integrity of
sensory perception as the receptor cells die and are replaced.
Continuity of perception across time must be maintained - challenge for smell and taste.
What are the requirements for a new taste cell and what is the lifetime of a taste cell
The new taste cells must express the same receptor and the processes must
connect appropriately. TCs live 30 – 60 days
How many odourant receptors does an olfactory neuron express?
Each olfactory neuron (ON) expresses only one odorant receptor
What are the requirements for a new olfactory neuron and what is the lifetime of an ON
New olfactory
neurons must express the same receptor and innervate the correct glomerulus. ONs live 10 – 20
days
Via what cranial nerves does taste info enter the CNS and what does it synapse onto?
Taste information enters the CNS via cranial nerves VII,IX and X and synapses in
nucleus tractus solitarius (NST) in the hindbrain.
Where does the nucleus tractus solitarius (NST) project
NTS projects to insular (taste) cortex via the thalamic nucleus VPM. Insular cortex also projects back to NTS via the hypothalamus and amygdala
(recurrent).
Taste papillae
anatomically arrayed on the tongue/. Taste receptors in fungiform papillae (taste receptors innervated by N. VII) are at the front, and those innervated by
circumvallate papillae (N.IX) at the back. The receptors of N.X that carry taste info are in the epiglottis.
The taste bud includes
taste cells and basal cells (taste stem cells)
The endings of cranial nerves 7,9 and 10 receive input from…
the endings (gustatory afferent axons) receive input from taste cells
How do taste cells respond to tastants?
The taste cell responds selectively to tastants that are salty, sweet, bitter and sour.
Which
tastants directly interact with ion channels?
Salts, acid (sour)
Which are transduced by G protein coupled
receptors?
Sweet, bitter, umami (amino acid)
What do all taste cells release
All tastants release ATP.
What do sour-detecting cells also release besides ATP
The sour-detecting cells also release serotonin.
What molecules help maintain the fidelity of the coupling between taste cells and afferent fibers
maintained by the same molecules that guide developing axons: the semaphorins. Semaphorins support labelled line for sweet and bitter when taste cells turn over. Facilitates aspects of connectivity.
Two potential microcircuits for detecting taste
cross fiber and labelled line
Cross fibre microcircuit
Response in number of different neurons –> one decoder neuron receives converging input from defined set of pre-S neurons –> sensation of sweet.
Labelled line coding
Sweet receptor –> sweet post-S neuron –> CNS
Which microcircuit is used in taste detection
labelled line coding
To determine which cell bodies of which cranial nerve ganglion carry taste information, you could place rhodamine labelled retro beads into the ____________ and look for labelled
cells in the __________ ganglia.
cNST (caudal part of NST); vagal ganglia, geniculate ganglia, glossopharyngeal ganglia
(corresponding?)
Control = infection into cuneate nucleus which has somatosensory info.
The central pathways through which tasted information reaches the forebrain are very similar in rodents and in man except that in humans taste reaches…
the orbitofrontal cortex
Incoming afference from 7,9,10, going into NST, which goes forward into VPMpc (thalamic nucleus), then forward into IC, then in humans goes into orbitofrontal cortex OFC. Has not been detected in the mouse.
In mice, what circuit motif resembles that between the hippocampus and entorhinal cortex?
Recurrent circuit; Recurrent circuits often found in parts of brain involved in memory and learning. Recurrent circuits once activated will continue to activate which maintains the pattern that was initially present in the connection between stimulus and emotional event (between taste and sweet – positive).
What kind of inputs can modify behavior responses to tastants in the brainstem of mice?
Top down innervation; can influence the perception of taste
You can activate bitter and sweet neurons in the brainstem to evoke bitter and sweet perception using…
Channelrhodopsin - channels which are sensitive to light; can open and activate a neuronal response or close and inhibit neuronal response. Effecting output of cells within the CNS.
So, can activate cortical neurons in the labelled line for bitter response, and if bitter tastants are supplied to mouse, bitter response in brain cell is enhanced. If activating neurons in bitter cortex/labelled line, you can suppress response to sweet tastants.
Taste sensors in gut vs tongue
In tongue, sweet neurons are responsive to both real and sugar and artificial sweeteners. In gut, only respond to actual glucose.
Sensory info from the gut travels via what nerve
Vagal nerve, CN10. Info travels this way into the CNS and into the NST.
Extensive representation of your body in the brain – thru tongue and internal state within intestinal tract.
Taste cells in the gut also respond to
Fat
Satiety
Brain knows how many calories you getting – satiety.
Brain also carries info on the fat content you’re getting, coming thru GRP40 and 120.
Taste sensation from the gut is essential to create feeling of satiety.
Taste circuit
Gut info comes thru the hepatic portal vein and the intestine into the cNST. From there you have the affective quality system - VTA and SNPc, which contain neurons that have dopamine (reward). SNPc only active when signals are received after actually eating, VTA also responsive to tastants as well as those signals.
All goes up to taste cortex. Both the info quality of tastants and also effective quality.
The rewarding qualities of taste are conveyed by the Substantia nifra and the ventral tegmental area which both include neurons that release the neuromodulator…
dopamine
Which order of mammals does NOT have a functional vomeronasal (VNO) system?
Primates
Difference between main OS and accessory (VNO)
Main OS uses ciliated OSNs, in olfa epithelium in the nose. VNO has microvilli OSNs. Have different family of receptors
VNO
Generally thought of (VNO) conveying info via pheromones. Closely tied to detecting smells of other animals and inferring their social state from their smell + individual ID.
Main system – conveying smells from environment/info from environment.
Where are the olfactory and taste systems derived from
OS and taste system derived from placodes (epithelial structure on surface of develop embryo give rise to peripheral neurons); also give rise to neurons that give rise to neurons that are actually going to migrate into the brain and secrete GnRH (released into blood system that goes between the hypothalamus and pituitary, stimulates the pituitary to release GnTR, goes to gonads, stimulates them to release T and Oestrogen.
Are ONs replenished?
Olfatory neurons continue to be born throughout development and migrate into interior olfactory tract. System geared to replace neurons that are worn out (1º or ones that they innervate).
How is the AOB organised
Topographically
Which molecules ensure info continues to travel to appropriate place within the OB?
Same molecules involved in axon guidance during development are involved in ensuring info continues to travel to appropriate place within the OB.
Slit molecules – repellent. Ephrin molecules – attractive.
Neurons expressing Robo, eg., repelled by slit. So innervate posterior OB. Neurons expressing Ephrins are anterior.
The hypothalamic circuit activated by the vomeronasaly-expressed receptor Vmn2r53 is experience-dependent. What kind of experience? What does this suggest about VNO-activated circuitry?
Social experience, specifically aggressive experience. Activate these neurons in animals that has social experience, could enhance aggression shown by these males.
Suggests Experience-dependent modulation; interaction between primary sense (nasal organ being activated is by part olfactant) and prior experiences. Social experience is a cognitively challenging area; and vomeronasal organ interacts with experience to promote appropriate social behaviour.
What does ESPN (a pheromone in mouse tears) do to female mice?
Suppresses sexual behaviour in female mice when expressed from the lacrimal glands of pups. So females spending a lot of time with pups have suppressed sexual behaviour, rearing offspring.
VMH (ventromedial nucleus of the hypothalamus)
important for sexual behaviour.
VNO system is contributing to the appropriate behavioural response of females depending on their experience and endocrine state. dVMH (activated by medial nucleus of amygdala MeA) –> sexual enhancement; vlVMH (normally inhibited by BNST, which is inhibited by MeA/AOB) –> sexual suppression.
Specificity of the main OS
Very chemically specific: enantiomers produce different smell percepts.
Also can have concentration dependent perception.
Odorants have highly specific effects in activating parts of CNS (pleasant vs. unpleasant).
How do ONs enter the brain
Olfactory neuron
Axons travel through
the cribiform plate (bone) to
enter the brain (olfactory
bulb)
The axons of olfactory neurons located in the turbinates inside the nose travel through this bone to enter the olfactory bulb.
Odorant receptors are located on which part of olfactory neurons
–> processes in the olfactory mucosa
Each ON only receptors one of each ORs. OR expressed on cilia of ORNs. Cilia extend into olfa mucosa, coated in mucus.
Olfa neuron is both a primary sensory neuron (detects the quality sensed), it is also a neuron, sending axons into the brain through the holes in the cribiform plate. Stem cells replace the cell they are in contact with
Stem cell replacement of ONs process
Olf epithelium stem cell nucleus, expresses Lamin-B receptor on the outside; around the nucleus you have heterochromatin. Then goes thru differentiated process into mature OSN expressing only one receptor. There is a super enhancer as a result of heterochromatic core within the nucleus and also the heterochromatic OR compartments, so only one of them is not shut down and it serves as an effective enhancers –> greek islands, determines with OR you express.
Primary olfactory neurons express only one olfactory receptor. What does the response of these neurons to mixtures of odorants suggest about their computational capacities?
Combinatorial. While each ON expresses only one receptor, the other odorants in a mixture affect the response of that neuron. So a combinatorial.
Saw this by looking at large fields of neurons across time–> Scape. Loaded all of these ONs with molecule that fluoresces when the receptor is there, can record across this entire area the response of individual Ons to odorants – single or combinations. Can assess the pattern.
All of the axons from an ORN converge on
A single glomerulus in the olfactory bulb.
Highly convergent system in which you have these plunging into the same area; input field is arrayed in heterogenous way but all ORNs coming into particular glomerulus.
Convergence
microcircuit motif. Feedforward excitation.
Where do ONs go after glomeruli; output is mitral cells. Their synaptic targets of mitral cells. LOT contains axons of mitral cells. ENT – input into the hippocampus.
If you were to put fluo tracer into OB, would discover that, if looking in PIR, you have huge expansion of the representation in PIR from the OB. There is convergence from the mitral cells into glomerulus, then you get into PIR and there’s expansion.
What are the targets of axons of mitral cells ?
are the anterior olfactory nucleus., the accessory olfactory nucleus, the piriform cortex, the entorhinal cortex and the cortical amygdala
what is DTI
magnetic resonance imaging to see major tracts in the nervous system (tractography). Relies on the fact that water molecules line up in axons; thin skinny lines are bundles of axons. Can start out with seed and follow tracts all the way back from there.
DTI = Diffusion Tensor imaging.
What 2 very surprising results about the axonal trajectories of olfactory bulb neurons in dogs were revealed by DTI
Surprisingly, see fibers that were travelling from OB all the way to SC (olfactory-cotico spinal connections). Do not see this in mouse. Real shock though is the fibers that travel from OB to occipital cortex (visual info).
Somatosensation
The brain receives input from the entire body both exteroceptive (stimuli from the outside) and interoceptive (stimuli from the inside); stimuli of which we are aware (touch or a stomach ache) and stimuli that we are not directly aware of (blood pressure, nutrients). Information from the body surface (somatosensation) is carried into the CNS via the processes of dorsal root ganglion cells (DRGs; body) and the trigeminal (V) and facial (VII) ganglia (face). Sensory information from the viscera (pain) travels rostrally and synapses in the contralateral dorsal column nuclei (cuneate and gracile) before travelling rostrally to the thalamus (VP) via the medial lemniscus and then on to insular cortex.
Sources of input to the brain in somatosensation
Skin, visceral, blood vessels
The brain receives info from the rest of the body (interception) in several ways
Afferents: cranial nerves and spinal nerves
Circulatory system: oxygen, CO2, hormones, glucose
The brain also receives information via its blood vessels. Many substances are excluded from these vessels by the blood brain barrier (endothelial cells whose processes wrap around the vessel walls).
Blood brain barrier
endothelial cells whose processes wrap around the vessel walls.
What were Patapoutoan and Julius aware the Nobel Prize for in 2021
Discovery of receptors for mechanosensation (touch) and pain.
The receptor for pain
The receptor for pain belongs to a family of TRPs (transient receptor potential), members of which also sense tastants. The pain receptor is the same as the receptor for spicy food (the capsaicin receptor - TRPV1).
The receptor for touch
The receptor for touch in vertebrates is called Piezo; its structure facilitates stretching of the cell membrane in response to applied pressure.
Molecular structures of TRPA1 and Piezo
TRPA1 - 123 Å long and 104 Å wide.
Piezo1 - 155 Å long and 200 Å wide.
There are many different kinds of touch
Texture, wind/air movement, soft touch (like fur), pressure/indentation
Difference between smooth (glabrous) and hairy skin
Smooth (glabrous) and hairy skin contain different touch receptors. Smooth skin has free nerve endings plus nerve endings encased in capsules: Pacinian corpuscles, Merkel cells, Ruffini corpuscles.
Smooth skin - Merkel cells – shape and texture perception, small receptive field, more superficial; Meissner capsule – motion detection, grip control, small receptive field, more superficial; Pacinian corpuscles – perception of distant events thru transmitted vibration, large RF, deeper in skin; Ruffini – tangential force, hand shape, motion direction, large RF.
The hairs on hairy skin move and amplify the sensitivity the nerve endings. Free nerve endings also wrap around touch domes, different kinds of them, but skin is particularly sensitive to touch. Free nerve endings start in the dermis, more superficial than those in the smooth skin, then extend into the epidermis.
Hairy skin – tactile stimuli are transduced thru variety of mechanosensory afferents innervating diff types of hair follicles. Pressure and movement of hair follicles activates these endings.
The touch and pain pathways as they ascend towards brainstem
The two pathways from the spinal cord travel rostrally in the ipsilateral (same side) dorsal column or cross in the spinal cord and then travel rostrally in the anterolateral pathway. In the caudal brainstem the dorsal column axons innervate the gracile and cuneate nuclei and then cross.
In what ways do the touch and pain pathways allow for localisation of the site of spinal cord lesion?
The different paths taken by touch and pain information from the lower body to the brain allow localization of the site of spinal cord lesion upon neurological examination.
Touch info ascends ipsilaterally in the dorsal columns, innervating the gracile and cuneate nuclei at the top of the spinal cord before crossing over at the caudal medulla and ascend to contralateral thalamus. Pain info crosses over immediately at level of the spinal cord then ascends in anterolateral system/column, which has diff set of pathways - first order neurons terminate in the dorsal horn, and second-order neurons send their axons across midline and ascend on contralateral side of cord.
So, lesion of the spinal cord would result in loss of sensation of touch, pressure, vibration and proprioception (dorsal column-medial lemniscal symptoms) on ipsilateral side of the lesion and loss of pain and temperature perception on contralateral side of the body.
How is a somatotropin map of the body maintained throughout the pathway from the periphery
A somatotopic map of the body is maintained throughout the pathway from the periphery , through the thalamus (VPL for body; VPM for face) to the somatosensory cortex.
DCN post-S neurons represent the body.
Somatosensory information from the face travels into the brainstem via cranial nerves
via cranial nerves V and Vii (5 and 7). They deliver info from different parts of the face. Vii also carries taste info (along with 9 and 10).
Touch information from the face is also processed in the VPM nucleus of the thalamus.
How do Piezo channels facilitate touch sensation
Touch opens pore, uses wings on the Piezo receptor to do that. Then allows ions to flow thru.
Slowly adapting and rapidly adapting receptors for touch
Merkel cells associated with nerve endings adapt slowly to touch;
Merkel cell adapts very slowly, burst of Aps at beginning of touch, and then they slow down (adapt).
Nerve endings associated with Pacinian corpuscles adapt rapidly and are particularly sensitive to vibration.
Pacinian corpuscles adapts rapidly, get action potential at beginning and end of touch, and vibration will elicit AP for every vibration movement.
Merkel cells and hair
Hairs amplify Merkel cell outputs
Merkel cells surround hair. Different sensation in hairy and smooth skin because of the endings.
Whiskers
Whiskeras are special hairs.
There is a cortical representation of whiskers = barrels
Barrel fields
Barrel fields are found in layer 4 of the appropriate part of somatosensory cortex.
Distinct patches of neural activity, each corresponding to a single whisker, can be visualised in layer 4.
The barrels can be visualized with cytochrome oxidase (this was the way Margaret Wong Riley discovered the color blobs in visual cortex). When cells fire a lot, the level of cytochrome oxidase really increases, which we can visualise. Barrel fields were discovered using 2D-oxyglucose.
Role of whiskers in rodents
The whiskers on the face of rodents amplify somatosensory information detected by the face and are represented by “barrels” in the face area of somatosensory cortex whose positions correspond to individual whiskers. Rodents with extra whiskers have extra barrels in the appropriate place
Thermosensation vs. nociception
While pain can be induced by intense heat, nociception is distinct from thermosensation and accesses different sensory pathways.
Pain neurons also express VR1 receptors.
Pain pathway and emotion
Pain pathways engage brain areas associated with emotion (amygdala, ACC etc).
A hypothetical pathway via which soft touch might access reward pathways in the mouse brain
The receptive field coming in on the neurons that express Mrgprb4 in DRG; travels forward, coming up to PAG. The PB nucleus also projects to PAG, so maybe input from here too. Goes forward to PVN, which then projects to VT nucleus, which is part of intrinsic reward pathway. Those neurons (which make dopamine) project forward to NAc.
Primary sensory neurons of the visual system
Rods and cones
Rods and cones (the cells in the retina that detect light) are highly specialised neurons. Rods support photopic (black and white) vision and cones support scotopic (color) vision. The relevant detector proteins (opsins) are located in the disks that comprise the outer segment. Disks get “used up” and are shed (phagocytized). The inner segment includes lots of mitochondria (enegy for restoring the membrane potential via ion pumps) . Distal to the compartment including the nucleus are the synaptic terminals (see below).
How does light travel thru layers of the retina
Layers of cells – output cells of the retina are RGCs, closest to the source of the light, and their axons form the optic tract which travels into the brain. Circuitry is like a mini brain. Eye is the mini brain.
Circuitry in the retina
Circuitry in the retina: photoreceptor layer which includes the outer segments, the outer nuclear layer, the plexiform layer. Layer of cell bodies and their processes, then a synaptic layer. Horizontal cells synapse on both the axons of photoreceptors and also synapse on the dendrites on bipolar cells. The horizontal cells transmit horizontal info, play role in contrast, lateral inhibition.
Bipolar cells are pass thru cells. Then come to lateral transmission mediated by amacrine cells, then finally get to RGCs which send info into the brain.
ON-centre ganglions vs OFF-centre ganglions
ON-centre cells increase their discharge rate to luminance increments in the receptive field centre, whereas OFF-centre cells increase their discharge rate to luminance decrements in the receptive field
What do recordings from the optic nerve reveal
RGC neurons have circular receptive fields: “on center” or “off center”.
If you shine light on centre of receptive field, get a lot of Aps. If you make that spot bigger, the number of APs goes down, and if you make it even bigger, it goes down more.
Centre-surround receptive field.
Responses of on-center and off-center retinal ganglion cells to spots of light and dark
The spot of light excites on center RGCs and inhibits off-center RGCs.
Inhibitory interneurons, horizonal cells, reduce transmission of APs in the processing units that are not in the centre of the receptive fields such that there are fewer APs coming out of the ganglion cells on the far left and far right RGCs because of the inhibition of the horizontal cells. Sharpens the perception of the receptive field and help create boundaries between centre and surround receptive fields of neurons in the RGC axons.
Starburst amacrine cells
confer motion sensitivity on direction selective RGCs. Don’t have any axons, just release GABA from their dendrites onto dendrites of RCGs.
Circuitry involves delay line between Neuron A and synapse on Neuron B. Neuron with X in it is coincidence detector. Delay gives directionality to the preferred direction of the starburst amacrine cell.
Three pairs of extraocular muscles insert onto the eyeball and stabilize gaze
The lateral and medial rectus muscles, the superior and inferior rectus muscles and the superior and inferior oblique muscles. Each is innervated by axons from a specific cranial nerve (III, IV and VI).
Head moves all the time, and all of the receptors are in your retina, very important to maintain your focus so that fovea is pointing at thing you want to look at. Maintaining foveation is due to muscles that insert into eyeball. Rectal muscles. All of these muscles move your eyeball with great sensitivity; innervated by motor neurons in cranial nerve nuclei.
Part of the circuitry for visual attention, to be able to tell what’s important in the environment.
Different kinds of photoreceptors project to different post-S cells within the LGN.
LGN has 6 layers, some of which get input from ipsilateral and contralateral eye. 2 kinds of cells, magnocellular and parvocellular (smaller). In-between them, there are koniocellular layers, white because the cells bodies are sparse.
Colours are represented initially by the responsiveness of the cones to wavelengths of light, then conveyed by the RGCs to the LGN.
Cortical organisation
Cortical organization is columnar. Columns go from dorsal to ventral surface. Diff cell types fround in different layers. Layer V – pyramidal neuron with apical dendrite going up to superficial layers, and basal dendrites further down, axons going to SC, pons etc. Other neurons that connect within the cortex on the same side, cell bodies more superficial. Neurons with input going back into the thalamus. Input coming in from thalamus coming into layer IV.
What do the results in Fig. 2A and B suggest about the receptive field of neurons in IT Cortex?
Areas within IT cortex that are sensitive to faces. Face cells.
Which hair cells (inner or outer) express the stretch activated channel that serves as the hearing receptor? What do the other hair cells do? How?
The inner hair cells express the stretch activated channel – they are the auditory organ. The outer hair cells are essential for the amplification of sound and control the tension on the basilar membrane. They act like muscles and are innervated by the efferent axons coming in which convey commands from the brain for the hair cells to expand and contract (don’t convey sensory info). The nerve terminals that contact inner hair cells are labelled as afferent because those fibres that are innervated by the inner hair cells which release glutamate in response to sound.
Shearing force
Stereocilia impacted by the movement of the tectorial membrane relative to that of the basilar membrane; tectorial membrane lies on top of the outer and inner hair cells. So if tectorial membrane is moving up because the basilar membrane is moving up, there’s shearing force of stereocilia, and they are pushed over from left to right. Stereocilia are not symmetrical.
When basilar membrane is in downward moving phase, stereocilia move in the opposite direction due to shearing force.
Shearing force is what’s responsible for transducing sound energy into the firing of axons within the inner hair cells.
In what way is the depolarisation of the inner hair cell asymmetric?
Movement towards the longer stereocilium stretches the tip link activating the “hearing receptor”. Movement in the opposite direction closes the channel.
Channel functions as a dimer.
