Key takeaways U2 Flashcards
1
Q
What is one challenge for both taste and smell neurons
A
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.
2
Q
What are the requirements for a new taste cell and what is the lifetime of a taste cell
A
The new taste cells must express the same receptor and the processes must
connect appropriately. TCs live 30 – 60 days
3
Q
How many odourant receptors does an olfactory neuron express?
A
Each olfactory neuron (ON) expresses only one odorant receptor
4
Q
What are the requirements for a new olfactory neuron and what is the lifetime of an ON
A
New olfactory
neurons must express the same receptor and innervate the correct glomerulus. ONs live 10 – 20
days
5
Q
Via what cranial nerves does taste info enter the CNS and what does it synapse onto?
A
Taste information enters the CNS via cranial nerves VII,IX and X and synapses in
nucleus tractus solitarius (NST) in the hindbrain.
6
Q
Where does the nucleus tractus solitarius (NST) project
A
NTS projects to insular (taste) cortex via the thalamic nucleus VPM. Insular cortex also projects back to NTS via the hypothalamus and amygdala
(recurrent).
7
Q
Taste papillae
A
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.
8
Q
The taste bud includes
A
taste cells and basal cells (taste stem cells)
9
Q
The endings of cranial nerves 7,9 and 10 receive input from…
A
the endings (gustatory afferent axons) receive input from taste cells
10
Q
How do taste cells respond to tastants?
A
The taste cell responds selectively to tastants that are salty, sweet, bitter and sour.
11
Q
Which
tastants directly interact with ion channels?
A
Salts, acid (sour)
12
Q
Which are transduced by G protein coupled
receptors?
A
Sweet, bitter, umami (amino acid)
13
Q
What do all taste cells release
A
All tastants release ATP.
14
Q
What do sour-detecting cells also release besides ATP
A
The sour-detecting cells also release serotonin.
15
Q
What molecules help maintain the fidelity of the coupling between taste cells and afferent fibers
A
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.
16
Q
Two potential microcircuits for detecting taste
A
cross fiber and labelled line
17
Q
Cross fibre microcircuit
A
Response in number of different neurons –> one decoder neuron receives converging input from defined set of pre-S neurons –> sensation of sweet.
18
Q
Labelled line coding
A
Sweet receptor –> sweet post-S neuron –> CNS
19
Q
Which microcircuit is used in taste detection
A
labelled line coding
20
Q
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.
A
cNST (caudal part of NST); vagal ganglia, geniculate ganglia, glossopharyngeal ganglia
(corresponding?)
Control = infection into cuneate nucleus which has somatosensory info.
21
Q
The central pathways through which tasted information reaches the forebrain are very similar in rodents and in man except that in humans taste reaches…
A
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.
22
Q
In mice, what circuit motif resembles that between the hippocampus and entorhinal cortex?
A
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).
23
Q
What kind of inputs can modify behavior responses to tastants in the brainstem of mice?
A
Top down innervation; can influence the perception of taste
24
Q
You can activate bitter and sweet neurons in the brainstem to evoke bitter and sweet perception using…
A
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.
25
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.
26
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.
27
Taste cells in the gut also respond to
Fat
28
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.
29
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.
30
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
31
Which order of mammals does NOT have a functional vomeronasal (VNO) system?
Primates
32
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
33
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.
34
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.
35
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).
36
How is the AOB organised
Topographically
37
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.
38
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.
39
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.
40
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.
41
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).
42
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.
43
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
44
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.
45
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.
46
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.
47
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.
48
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
49
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.
50
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).
51
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.
52
Sources of input to the brain in somatosensation
Skin, visceral, blood vessels
53
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).
54
Blood brain barrier
endothelial cells whose processes wrap around the vessel walls.
55
What were Patapoutoan and Julius aware the Nobel Prize for in 2021
Discovery of receptors for mechanosensation (touch) and pain.
56
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).
57
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.
58
Molecular structures of TRPA1 and Piezo
TRPA1 - 123 Å long and 104 Å wide.
Piezo1 - 155 Å long and 200 Å wide.
59
There are many different kinds of touch
Texture, wind/air movement, soft touch (like fur), pressure/indentation
60
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.
61
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.
62
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.
63
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.
64
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.
65
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.
66
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.
67
Merkel cells and hair
Hairs amplify Merkel cell outputs
Merkel cells surround hair. Different sensation in hairy and smooth skin because of the endings.
68
Whiskers
Whiskeras are special hairs.
There is a cortical representation of whiskers = barrels
69
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.
70
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
71
Barrel representation
The barrel representation is present at all levels of neural processing from brainstem (hindbrain) through thalamus to cortex.
72
Area S1 in somatosensory cortex
Area S1 in somatosensory cortex (just posterior to the central sulcus) has a somatotopic map of the entire body with neural “space” inversely proportional to the size of typical, individual receptive fields.
The genital regions of male and female rodents are also represented in somatosensory cortex
73
How to find the receptive field of a somatosensory neuron you are recording from. Where? How big? Shape? Structure (e.g. center-surround)
Poke around to determine size, and map out the area of skin where you get a response.
Two point threshold, areas of skin where you can tell two points apart. Low when receptive field size is small, and high when receptive fields are large.
Poke around, find area, where you can record Aps.
74
Receptive field
Receptive field = Area of sensory space where stimulation changes the activity of the neuron that you are recording from (increasing, or if spontaneous activity, can change by decreasing).
75
Lateral inhibition
A circuit motif that sharpens contrast. Responsible for size of receptive field and ability to do 2-point discrimination in somatosensation.
Inhibition via interneurons which sharpen the receptive field.
Lateral inhibition in the visual system makes the grey lighter along along the line where it abuts the darker grey and makes the darker grey darker. This is a visual illusion.
76
Somatosensory cortex
Behind the central sulcus. Includes subregions (1,2, 3a, 3b) and well as SII (secondary somatosensory cortex).
77
Receptive field have structure
Can pick up inhibition in somatosensory cortex.
"Centre surround" organisation - E.g. an excitatory centre and an asymmetrically inhibitory surround. Touch in the inhibitory surround will result in inhibition/reduction in spontaneous firing of those sensory receptors/neurons. Lies to you --> makes things in the world more different.
78
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.
79
Injury also causers pain
injury to the skin promotes the release of many substances such as histamines, substance P, prostaglandins etc that excite pain receptors. Mast cells release substances that excite MRGPR pain receptors.
80
First pain vs second pain
First (epicritic) pain information is carried into the dorsal horn of the spinal cord by A-delta fibers (myelinated) and second (protopathic) pain by C fibers (unmyelinated) - end up in the most dorsal part of dorsal horn (layers 1,2).
So difference in speed of transduction. First pain travels fast, while second pain (long-lasting) travels slowly. Both express TRPV1.
81
MRGPRs
MRGPRs always thought to be for pain, but also convey soft touch via another pathway, so no intrinsic ability to do one thing or the other.
82
Pain pathway and emotion
Pain pathways engage brain areas associated with emotion (amygdala, ACC etc).
83
Descending control of pain
Pain can be blocked by activating inhibitory neurons in the spinal cord either locally or via descending pathways (the “Gate Theory”). Pain is a “neural construct”.
Why we rub a painful spot, to activate local inhibitory neurons in sc.
84
Liu et al (2017) knocked the gene coding for placental alkaline phosphatase (PLAP) into the MRGPR locus to determine where these receptors were expressed. What did they observe?
Discovered the receptor is only in hairy skin. There are these receptive patches, which represent the receptive field and can figure out how big it is. 3D receptive fields, and the size corresponds very closely to the size of the patches. Speculate that it might be associated with soft touch.
85
What were Liu et al's findings regarding PALP+ cells in DRG and MGRP receptors?
Cells in DRG that were PALP positive were unmyelinated (i.e C) fibers in the thoracic nerve. Two different MGRP positive processes innervating hairy skin. Authors suggested that these receptors might mediate soft touch.
86
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.
87
What is a sensory system?
All sensory systems have detectors. Detectors = receptors.
Detector: outside world (extero), inside the body (intero), movement associated (proprio)
Same stimulus can activate multiple detectors
Decoders: representation of stimulus features in neural activity - involves microcircuits.
Sensory circuits: groups of neurons whose interactions create distinct representations of stimuli. Representations can be of different aspects of the stimulus – e.g. colour and intensity.
Sensory systems: interconnected circuits that create internal representations of the external and internal worlds
Overview: Can be either extero- or interoceptors. Includes detectors (e.g. photoreceptors), decoders (e.g. rods or cones), circuits (e.g. the retina) and systems (e.g. the visual system).
88
Visual illusions
Visual illusions are graphic examples of the observation that our perception of the outside world (or the inside world for that matter) are not “real” but instead constructs created by our nervous system. The heightened contrast between dark and light “edges” is an example of a simple illusion. This example is a complex illusion involving the cues for visual motion.
89
Where does the eye come from - retina
The optic vesicle originates from part of brain that was going to turn into forebrain. Includes the neural retina. Early on forms a cup, eventually turns into the eye.
The retina is an outpouching of the developing neural tube (the region that will become the diencephalon). This developmental history suggests that the retina is a sort of “minibrain”; visual information leaves the retina (via the optic nerve) already highly processed and not just a passive reflection of the visual scene.
90
Where does the eye come from - lens
Neural tube induces the lens from overlying ectoderm
The lens develops from an inductive developmental interaction between the retina and the overlying epithelium; invaginates, optic cup wraps around it, and lens pinches off to form lens vesicle. Area just outside will become cornea of the eye. Inner layer has light sensitive elements, including RGCs, whose axons go into the brain to convey visual info.
91
Fovea
Has the highest density of photoreceptors (mostly cones). All the way at the back of the retina.
Thus supports high acuity (ability to tell one small thing from another) vision. One of the reasons why “foveating” is a market for attention is that it represents the motor act of focusing attention on a small part of the visual field.
92
RGCs
towards the front of the inner layer, and their axons leave the retina thru the optic nerve – blind spot.
(one of the reasons for rapid eye movements; we do not ordinarily perceive this blind spot).
93
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).
94
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.
95
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.
96
Foveation
Maintaining the eye position to maximise visual acuity. Foveation – focusing eye on small part to bring cones in and have high acuity vision. Foveation is a form of attention, indicator that paying visual attention to something. Taken as proxy for cognition in species like nonhuman primates.
97
Location of retina
The retina is at the back of the eyeball and light must also travel through multiple layers of retinal neurons (including retinal ganglion cells or RGCs) before reaching the photoreceptors at the back.
98
Dark current
In the dark photoreceptor cation (Na+ and Ca++) channels are open so the membrane is depolarized creating the dark current. Neurotransmitters are released in the dark - glutamate.
These channels are closed in the light so membrane channels are hyperpolarized (no current flow), and rods and cones do not release glutamate.
99
How the do we sense light?
In the dark, photoreceptor cells have high [ ] of cGMP. cGMP binds and causes the opening of cGMP-gated ion channels, so NA+ flows into the cell and depolarises it.
When a photon hits the outer segment, it is absorbed by trans-retinal (the photopigment in the stacks' membrane and located in a pocket of the opsin), which bends the retinal and thereby activates the rhodopsin. Activated rhodopsin activates transducin (G protein in disc membrane), which diffuses and activates phosphodiesterase. Phosphodiesterase "chews" up cGMP, reducing its [ ]. The cGMP-gated ion channels close, reducing the influx of Na+. Since the K+ channels remain open, the cell hyper polarises.
Glutamate is no longer released by the rods/cones. This reduction in glutamate release has opposite effects on ON or OFF-centre bipolar cells due to expression of diff types of glutamate receptors. OFF-centre cells express inotropic receptors, so the cell depolarises in response to glutamate release. In the light, OFF-centre cells are hyper polarised and no longer release glutamate/innervate OFF-centre ganglion cells. ON-centre cells express G-protein coupled metbotropic glutamate receptor which hyper polarises the cell in the presence of glutamate. In the light, this hyper polarisation no longer occurs and the ON-centre bipolar cell is depolarised, and can release glutamate and depolarised the ON-centre RGC.
100
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
101
ON- and OFF-centre bipolar cells
The sign is flipped by on center and off center bipolar cells.
Photoreceptors that synapse with OFF-centre bipolar cells are sign conserving because change in MP of the bipolar cell is the same as in the photoreceptor.
ON-centre bipolar cells are sign inverting because the change in MP of bipolar cell is the opposite of that in the photoreceptor.
102
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.
103
What is the purpose of horizontal circuitry in the retina?
Horizontal circuitry in the retina (and elsewhere) enhances contrast”: at edges, light is lighter and dark is darker. Basically the idea is that neurons in the center of the pathway from a localized sensory stimulus will produce more action potentials than neurons from the “surround” (the adjacent areas). Inhibitory neurons contacted by surround neurons will be less effective (relative to strong excitation in the center) creating contrast.
--> horizontal cells do this.
104
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.
105
What do rods and cones release in the dark
Both rods and cones release glutamate in the dark. A spot of light reduces glutamate release. On center and off center bipolar cells respond in opposite ways to glutamate. Glutamate hyperpolarizes off-center bipolar cells and depolarized on center bipolar cells (“flipping the sign”)
106
How many kinds of RGCs are there
There are at least 20 different kinds of RGC in 3 main classes (midget, parasol and bistratified. M cells project to magnocellular layers of LGN, P cells to parvocellular layers and K cells to koniocellular layers).
Some of the RGCs are motion sensitive, respond to spot of light or dark moving across back of the retina.
107
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.
108
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.
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Circuitry underlying the vestibular ocular reflex
When the head moves to the left, both eyes move to the right to maintain the position of gaze.
There are hair cells in inner ear which deflect when you move your head to the right, and send inhibitory input to CN6, and excitatory input to the other side so that the direction of movement of eyeball is opposite to that of your head.
Used as a behaviour reflex in fUS paper.
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Uses of fUS
Can be used to look at connectome in the brain – stimulate one part and observe activity in another ; can be used to look at areas of brain simultaneously active. Can look at blood vessels; can be used in awake and freely moving animals, have to account for motion artifact. Can be used in newborns. Can be used to observe idiosyncrasies of human brains prior to surgery.
But useful of fUS imaging is that it has both great temporal and spatial imaging. Can get activity in real time because animal can be doing something while you’re imaging it.
High resolution, whole brain ultrasound can address multiple challenges in Neuroscience with better resolution (100 micra) than FMRI, and without having to implant electrodes into the brain.
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How does fUS work
fUS, using the Doppler shift create by transmitting a very short wavelength sound into the brain that hits a red blood cell in the vein or capillary and is reflected back at either a higher frequency (if red blood cell moving towards the sound source – echo; or down if moving away) doppler effect. Behaving like a bat.
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How is the receptive field of a neuron "mapped" and what determines whether you record a change in membrane potential or an action potential? The location of the electrode – in or near the RGC or its axon.
Receptive field of a neuron is “mapped”
by identifying the stimulus adequate
to change its activity: membrane potential
or action potentials
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RGCs vs starburst amacrine cells
Retinal ganglion cells tile the retina while starburst amacrine cells shingle the retina.
Two layers that influence firing – horizontal cell layers which communicate with multiple receptor cells; and amacrine cells which has similar kind of morphology in terms of its connectivity. RGCs tile the retina – represent every single point in visual space, with some larger and smaller receptive fields. All of what we are looking at is represented in the retina.
Starburst amacrine cells have receptive fields that overlap. Dendritic fields overlap significantly. These are the ones responsible for motion detection in the retina.
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Retinotopic map
Upper vs lower visual field – get inverted on back of the retina before they go to the brain.
Retinotopic map on the back of the eye that corresponds to what we’re seeing, and that map emerges from retina into the brain already highly preprocessed due to circuitry within the retina.
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Fovea in primary visual cortex
The fovea is overrepresented (takes up more space than the rest of the visual scene) in primary visual cortex (Area 17).
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What can be used to mark neurons activated by a particular visual stimulus?
2- deoxyglucose (2DG) and Fos (an IEG)
Cytochrome oxidase – increases its activity in neurons that are very active, can pick it up in histological stain, so can pick up pattern on flattened version of visual cortex.
Visuotopic map of what is in the outside world.
2-deoxyglucose and IEGs can also be used, all have to be used in post-mortem tissue.
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Receptive fields in periphery vs near the fovea
Receptive fields in the periphery are much large than in the centre due to density of photoreceptors. Fovea is over-represented throughout visual pathway, the periphery is underrepresented(?).
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How is visual info relayed to primary visual cortex (aka V1)
by the lateral geniculate nucleus (LGN).
Many of the axons cross at the optic chiasm. And the axons go onto a number of targets, superchiasmatic nucleus (circadian rhy), pretectum, and also superior colliculus. From there, will go both directly and indirectly to LGN, which gets input from both eyes.
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Visual cortex is located:
In the occipital lobe.
Primary visual cortex is at the back of the cortex. Info then gets shipped out to other parts of the brain.
A lot of visual cortex is actually on the inside of the sulcus, so hard to get at.
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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.
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Colour opponent cells and their location in the layers of the LGN
Red/green (but not colour contrast) = Parvocellular (4 dorsal layers, LGN layers 3-6).
Blue/yellow = Mostly parvocellular
Luminance contrast = Magnocellular (2 ventral layers, LGN layers 1-2).
Lavender/green = Koniocellular (LGN "in between" layers, white bc cell bodies are sparse).
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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.
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Hubel and Wiesel experiments
Neurons in the primary visual cortex respond selectively to oriented edges. (A) An anesthetized animal is fitted with contact lenses to focus the eyes on a screen, where images can be projected; an extracellular electrode records the neuronal responses. (B) Neurons in the primary visual cortex typically respond vigorously to a bar of light oriented at a particular angle and less strongly—or not at all—to other orientations. (C) Orientation tuning curve for a neuron in primary visual cortex. In this example, the highest rate of action potential discharge occurs for vertical edges—the neuron’s “preferred” orientation.
Cells are tuned to diff orientations.
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the geometrical relationship between columns in V1
Input from left eye and right eye alternate – ocular dominance columns. The area of the visual field are coordinated within the space, but there are stripes of right eye left eye.
Orientation columns move very smoothly as you go from one column to the next. Interspersed with these are groups of cells responsive to colour, “blobs”. If you put entire thing together, you have all dimensions of what these cells in V1 are responsive to.
Orientation and ocular dominance columns are parallel (?); same with orientation columns and blobs.
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Dorsal and ventral streams
For visual stimuli, dorsal processing streams focus on “where” the visual stimulus is and ventral processing streams focus on “what” the visual object is.
“What” goes from V1 down to inferotermporal cortex. “Where” pathway goes forward into region that has representation of areas in space.
There are connections between regions that are very sensitive to gaze/attention like LIP, and from frontal eye fields, which then project back, down thru synapses down to muscles that control gaze in space of the eye.
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Tanaka recorded from neurons in inferotemporal cortex. What do the results of responses to different views of a cat’s head suggest about their receptive fields?
Columns involved in receptive fields might interdigitate with other columns.
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What do the visual abilities of the patient being interviewed suggest about the nature of damage to visual processing areas in his brain?
The parcellation of functions within the visual stream processing.
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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.
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Using fMRI imaging and electrode recordings Doris Tsao (during her PhD research in Marge Livingston’s lab) discovered that...
“face cells are represented as patches in IT cortex.
These regions are on both the left and right hemispheres of the temporal cortex. The patches are highly selective for face cells, but embedded in regions also responsive to objects.
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How did the Tsao lab determine which characteristics of a face are particularly relevant in exciting face cells?
Parametised face space. Varies aspects of the face parametrically. Distance of the eyes from each other, the distance between the eyebrows etc.
Mapping receptive field for faces in IT cortex.
First had to figure out whether cartoon pics of faces would drive cells are all – get response to cartoon faces. Then varied that parametrically. How far apart eyes are, how close together eyebrowns are. If neuron doesn’t car, it fires anyway, if it cares, as you vary it, get slopes of reaction.
Recorded a bunch of face cells in response to pics, and took those and ran thru 50-d face feature vector function (up and to the right) and retranslated that back into the face.
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What is the connection between vision and cognition in primates (like us)?
Golman-Rakic suggests that inputs from regions in IT cortex that encode object identity have access to neural circuitry in prefrontal cortex that support working memory.
Many of these circuits are recurrent and hold great promise for things like attention and visual working memory.
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Auditory system
Sound is exteroceptive
Decoding begins with the hair cells of the inner ear
Delay tuned neurons in the auditory cortex help owls localize sound in space
The owl midbrain (superior colliculus) includes a multimodal map of auditory space; auditory cortex in humans includes circuit motifs for decoding speech.
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The McGurk effect
watching the lips of speakers move influence the auditory perception of the sound they produce
"auditory illusion".
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Near field vs far field
The vibrations from the tuning fork create a travelling wave consisting of alternating periods of compression and rarefaction (spreading out). The air molecules directly moved by the vibrating fork constitute the near field (actual molecules affected by tuning fork). Drosophila (the fruit fly) males vibrate their wings to produce a near field courtship “song” that attracts females. The far field is what we hear when we listen to another person, music etc.
Many sounds are created by vibration - membranes that vibrate when air goes thru them.
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Pure tone
The moving air particles are a travelling wave. A pure tone (eg 220 or 440 cycles per second or Hertz) is a sine wave.
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Oscillograph
A graph of sound pressure as a function of time (or distance).
x axis - time
y axis - air pressure/amplitude
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Sound frequencies
Hertz or cycles/sec
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What are the three parameters with which we describe travelling waves?
Amplitude (loudness), frequency (pitch), and phase are three parameters with which we can classify a simple sound wave
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Complex sound wave
Most naturally occurring sounds are complex, for example speech or music.
Communication signals and music: structured spectrotemporal features ties to identification and emotion
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Sound spectrogram
Vertical axis - Frequency
Horizontal axis - time
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What is the definition of an harmonic series of pure tones?
Integral multiples of the fundamental (lowest frequency).
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For a human listener, what difference in dB between two sounds is perceived as twice as loud? What the reference sound pressure level used in calculating decidels?
Each 10 fold increase in the amplitude of sound is perceived as being twice as loud; P ref is the absolute pressure of human hearing.
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Phase and angle
Gives you info about location of sound source.
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Ear anatomy
The outer, fleshy part of the ear is the ___pinna__; the ear canal is technically called the __external auditory meatus___; the three middle ear bones are the __malleus___, the __incus___ and the __stapes___. The auditory portion of the middle ear is the ____tympanic membrane___.
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The stapes inserts onto the
Oval window
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Where on the basilar membrane within the cochlea (relative to the oval window) are low frequency sounds represented?
Located on the “thinnest” part of the basilar membrane, so to the ‘right” when unraveled?
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Outer hair cells
Amplify sounds; necessary for normal hearing.
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Inner hair cells
Responsible for hearing; contacted by afferent axons of N8. They release glu.
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In cross section the cochlea includes three fluid filled chambers
the scala tympani, the scala media and the scala vestibuli. The hair cells and the basilar membrane are located between the _scala media_ and the __scala_tympani___.
Have diff ionic compositions.
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The tectorial membrane
lies over the __hair__ cells on the basilar membrane.
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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.
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Stereocilia
transduction mechanism for turning movement of basilar membrane and tectorial membrane above it, into sound frequencies.
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Rock around the clock. The music was converted into an electrical stimulation pattern and delivered to the outer hair cells. What does the behavior of the hair cells suggest about their role in audition?
The behaviour demonstrates the expansion and contraction of the outer hair cells, which suggests a role in controlling tension of the basilar membrane to which they are attached. Shows their motor function.
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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.
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What drives OHC motility at different frequencies
intracellular potentials drive OHC motility at low frequencies and extracellular receptor potentials drive OHC motility and cochlear amplification at high frequencies”.
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What is responsible for shearing force
The overlying tectorial membrane is responsible for the shear forces exerted on the strereocilia of hair cells as the basilar membrane move up and down in response to the travelling wave. Note the asymmetrical length of the stereo cilia.
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How the inner hair cell works
The tips of the stereocilia are connected by “tip links” that attach to the auditory receptor dimer (the “hearing receptor”: TMP1) and open it allowing positively charged ions to enter the cell and depolarize it. Calcium also enters the cell allowing fusion of synaptic vesicles with the membrane and depolarizing the post synaptic process from neurons in the spiral ganglion (CN VIII) by releasing glutamate.
Tip links stretch the membrane of the hair cell, which activates a cation channel, and the high [ ] of K+ in the fluid surrounding the hair cells travel in, depolarizing the hair cell. Glutamate is released.
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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.
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The stretch receptor
The stretch receptor that tip links access is TMP1/2, the hair cell "hearing receptor", basically a stretch receptor --> mechanoreceptor.
Highly conserved in mammals; a few residues that are different; clearly a very important receptor.
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Stereocilia and the coding for sound frequencies
Depolarisation is asymmetric, which is what codes for sound frequency. Stereocilia cannot move as fast as cycles/second that we can hear at. This asymmetry produces a gradual depolarization during high frequency stimulation; rates that the hair cell stereocilia cannot keep up with supporting hearing of high pitched sounds.
For high frequencies, you get a prolongued depolarization, so that the depolarisations accumulate, which signals high frequency. Low frequencies, the stereocilia can move back and forth quickly enough.
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von Bekesy
The travelling wave on the basilar membrane responsible for auditory transduction
There are complex frequencies in a sound; have to measure each frequency and see how loud to pull apart complexity.
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How do we characterise the responses of auditory neurons to sounds?
we deliver sounds of different frequencies (pitches) at different sound levels and record membrane or action potentials. First one generally delivers sounds across frequencies to see if the neuron responds to a particular pitch. Then the intensity of the sound is varied until the sound level that first induces a response in the auditory neuron is identified. This process reveals the best frequency for that neuron.
If the tuning curve is a vertical line we conclude that the neuron is a tightly tuned neuron, responds only to a single sound/pitch/frequency, doesn’t matter if low or high. Receptive fields like this don’t occur naturally, occur as a result of processing in the circuit, e.g. receptive fields like this in the back of the auditory cortex.
Most auditory receptive fields are V shaped, the lower threshold at one frequency, and as you go away from the best frequency, you need higher and higher intensity/loudness of sound to get the neuron to fire.
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How is the width of a tuning curve determined?
Mathematical measure of the sharpness of tuning curve – Q10dB. Centre frequency / width of tuning curve 10dB above detectable.
High frequency tuning curve is much narrower then low frequency tuning curve. Shoulder means responds pretty much the same to all these diff frequencies.
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Location of low vs high frequencies relative to the cochlear/basilar membranes
High frequencies are closest to the cochlear, low frequencies next to basilar membrane.
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Hair cells are innervated by processes of?
Hair cells are innervated by processes of N. VIII whose cell bodies are located in the spiral ganglion.
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As the eighth nerve axons enter the hindbrain...
The eighth nerve fibers split as they enter the hind brain and innervate the dorsal and ventral cochlear nuclei permitting parallel processing of each sound for different qualities.
First synapses made by auditory nerve are in the cochlear nucleus in the hindbrain.
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The DCN extracts
the spectral features of sound. The cellular composition of the DCN bears a more than passing resemblance to the cerebellum, especially in terms of parallel fibers and the many very small granule cells.
Fusiform cell - looks like structure in cerebellum.
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The VCN is specialized ...
for sound localization. The VCN includes Octopus (vowels, music clicks), Bushy (innervated by 10 cochlear nerve fibres, low input resistance, important for sound localisation) and Stellate cells (intensity coding, speech, implicated in tinnitus).
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The flow of information from the cochlear nuclei to primary auditory cortex (A1)
First projection to medial and lateral superior olives (some fibers cross to the other side; others ascent ipsilaterally). Second station to the lateral lemniscus then on to the inferior colliculus (inferior = auditory; superior = visual), on to the thalamus: medial geniculate nucleus (LGN is visual) and then to A1.
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DCN and self-generated sounds
DCN suppressed info coming fro mice's own licking.
Singla/Sawtell et al
Nate Sawtell and his lab discovered that cells in the DCN are insensitive to self-generated noise (licking) due to parallel fiber innervation..
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One mechanism for sound localization in mammals?
One mechanism for sound localization in mammals uses a contralaterally projecting inhibitory neuron in the LSO that projects to the medial nucleus of the trapezoid body (MNTB) which would otherwise excite cells in the ventral cochlear nucleus.
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Owls use multiple mechanisms to localize sounds in elevation and azimuth
One ear is higher than another helping with _localising the elevation of the sound. Auditory neurons can use phase angle to determine distance. A delay line (MEANDERING AXON) from the ipsilateral nucleus magnocellularis meets up with the much shorter axons from the contralateral nucleus magnocellularis in the nucleus laminaris transforming differences in arrival time into a spatial map.
NMDA receptor – used to detect the coincident arrival of sounds, is normally a cation channel plugged by Mg, and when membrane slightly depolarizes, Mg is kicked out, so next input can cause larger ESPS and result in AP.
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interaural time differences (ITDs) and interaural level differences (ILDS)
Information on interaural time differences (ITDs) and interaural level differences (ILDS) are sent to the owl auditory midbrain (IC). Visual information from the superior colliculus and auditory information from the inferior colliculus converge in ICX creating a multimodal space map.
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Taste cells in the intestines
There are taste cells in the intestine that respond both to sweet but also to sweet tastants with nutritional value like sugar vs. fat
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You are recording from a process of the vagal nerve just before it enters the hindbrain. What substance(s) would you use to determine whether the taste cell was in the gut or the mouth?
RetroRed.
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Experiments from Zach Mainen’s lab cued thirsty mice to alocentrically locate a port dispensing water using olfactory cues. Why didn’t they use egocentric (relative to the mouse’s body) cues?
Initiation port location was randomized and balanced across port blocks, which encourages rats to adopt allocentric strategies
