neural circuits Flashcards

1
Q

glutamate

A

excitatory neurotransmitter - promotes AP
binds to NMDA and AMPA receptors

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2
Q

glutamate receptors

A

ionotropic - AMPA, NMDA - ion channels, rapid changes in membrane potential

metabotropic - activate intracellular cascades, neuronal excitability and synaptic transmission

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3
Q

the nervous system

A

detects change, recognises change, executes specific behavioural problem

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4
Q

patch clamp methods

A

pipette based: high contact between electrode and cell - cell-attached recording method

planar: whole cell, no electrode, grow cell into hole

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5
Q

configurations of patch-clamp

A

cell-attached - single channel currents and dwell times

inside-out - removes membrane using pipette
intracellular environment (ions, channels, receptors)

outside-out - membrane exposed to extracellular environment = inside out patch - synaptic transmission and receptor kinetics

perforated-patch - agents create pores so ions can pass, access to intracellular components while maintaining membrane integrity

loose-patch - loose seal, minimises disruption, measures synaptic transmission

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6
Q

problem with patch clamp methods

A

cannot label many cells
limited ability to label specific cell type and live labelling

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7
Q

epifluorescent microscopes

A

function: stimulation of fluorescence by excitation light
dichroic mirror = reflect emitted fluorescence away from excitation light path

generates high contrast + resolution by using high numerical aperture objective lens

use of fluorescent dye = emits fluorescence at distinct wavelengths

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8
Q

difference between patch clamp and sharp electrode recordings

A

patch clamp = higher sensitivity of individual cells, higher spatial resolution

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9
Q

GFP

A

found in jellyfish

used to label cell membranes, visualise intracellular organelles, track gene expression and protein localisation

absorbs blue/ultraviolet light at a particular wavelength and emits green fluorescence through fluorescent

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10
Q

principles of GCAMP

A

protein of modified GFP and a calcium-binding protein and a third protein

it is a fluorescent and calcium-binding protein

when calcium binds, brings GFP closer = brighter fluorescence

good indicator of intracellular calcium levels

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11
Q

how does GCaMP indicate changes in intracellular calcium levels

A

changes fluorescence in response to calcium binding

neurons brighter when calcium levels rise

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12
Q

benefit of using confocal microscope

A

better resolution in z axis

uses pinhole to eliminate out-of-focus light

scans across specimen in a raster pattern

3D data sets

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13
Q

channelrhodopsin

A

peak absorption wavelength = 470nm

primary function in optogenetics = modulates membrane potential by allowing ion flow upon light activation

flow of sodium when light activates

permeable to sodium and potassium

exposed to light, influx of positive ions depolarises membrane = action potentials

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14
Q

halorhodopsin

A

stimulated by yellow light

transmits chloride (hyperpolarisation)

inhibits neuronal activity and making the neuron more negative than resting potential

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15
Q

cajal and Golgi dye

A

cajal = fine details of dendritic trees
Golgi dye = labels neurons sparsely

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16
Q

issues of enhancer traps

A

cannot stain individual neurons
cant combine morphological and electrophysiologicology of same cell

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17
Q

sharp electrode recordings

A

records changes in membrane potential = action potentials

disadvantages:
1. no solution change in or out of cell
2. limited possibility for controlling MBP due to depolarisation
3. cannot measure single channels

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18
Q

visual system - 3 types of stimuli

A

food
predator
mate

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19
Q

two main pathways of visual system

A

ventral (information) - from V1 to temporal lobe
dorsal (localisation) - from V1 to parietal lobe

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20
Q

lateral geniculate nucleus

A

thalamus

relays information from retinal ganglion cells via optic nerve and tract to V1 cortex

layers = magnocellular (light), parvocellular (colour, fine detail), koniocellular

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21
Q

retina components

A

pupil - regulates light

lens - focuses images onto fovea

fovea - highest visual acuity, no rods many cones

optic disk - natural blindspot

ganglion cells

bipolar cells - connect photoreceptors and ganglion

rest - photoreceptors at the back - lower acuity with rods + cones

horizontal cells - receive input from photoreceptors

amacrine cells - receive input from bipolar cells

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22
Q

feedforward neurons

A

photoreceptors (rods (dim) and cones (bright))
bipolar cells (glutamatergic so release glutamate)
ganglion cells (output cells)

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23
Q

feedback neurons

A

horizontal (inhibitory)
amacrine cells

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24
Q

layout of retina

A

3 layers of neurons
2 layers of synapses

photoreceptor layer (outer nuclear layer)
inner nuclear layer - bipolar, horizontal, ganglion
ganglion cell layer

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25
Q

on cells

A

light = less glutamate into bipolar cells
depolarise

ON bipolar cells depolarise activating ON ganglion cells

centre surround organisation

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26
Q

off cells

A

don’t generate action potentials when light flashes
hyperpolarise

don’t use iontropic ampa receptors - use metabolic glutamate receptors (mGLuR)
removal of cGMP not required for channel closure

OFF bipolar cells depolarise is dim light and activate OFF ganglion cells

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27
Q

inner plexiform layer

A

layer of synapses
four synapses between bipolar, amacrine and ganglion cells

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28
Q

receptive field

A

area of retina when illuminated activates a visual neuron

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29
Q

centre-surround organisation

A

illumination of the center leads to responses in opposite polarities = DEPOLARISATION

due to glutamate release from photoreceptor cells

inhibitory surrounding - input from horizontal cells releasing inhibitory neurotransmitters onto bipolar cells = HYPERPOLARISATION

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30
Q

types of ganglion cell

A

parvocellular - small dendritic trees and small receptive field with centre surround organisation

magnocellular - larger receptive field and dendritic trees, reacts to different colours

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31
Q

rods

A

activated by dim light
more cyclic GMP

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32
Q

cones

A

activated by bright light

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33
Q

phototransduction

A

light causes reactions in photoreceptor cells

activate g-coupled protein receptors and phosphodieterase

hydrolyses cGMP to GMP

decrease in intracellular cGMP

non-selective channels close = hyperpolarisation

reduces release of glutamate = electrical signals

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34
Q

important features of sound

A

encodes:
sound frequency - cycles per second (10(3))
sound intensity - range = 10(12)
onset - helps localise
duration

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35
Q

3 chambers of cochlea

A

scala vestibula - perilymph (low potassium, normal calcium, high sodium)

scala media - endolymph (high potassium, low calcium and sodium - endocochlear potential = +80mV

scala tympani - perilymph

cochlea spiralled to extend hearing frequency range and fit more sensory cells

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36
Q

organ of corti

A

sensory hair cells
connections frome nerve fibres to auditory nerve
on basilar membrane

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37
Q

hair cell resting gradient

A

-60mV

electrical gradient of 140mV between scala media and hair cells (vital for function)

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38
Q

how sound stimulates sensory hair cells

A

wave enters ear

passes into cochlea creating a travelling wave along the basilar membrane

sound of frequency causes maximal movement of basilar membrane at a location = characteristic frequency location

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39
Q

lower vs high frequency sound

A

low = travels further and maximal movement towards apex

high = travels less and causes maximal movement to the base
low energy

= tonotopically organised (high at base, low at apex)

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40
Q

place frequency code

A

brain interprets position of active inner hair cell as a specific sound frequency

Neural firing rate used to encode sound intensity

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41
Q

inner hair cells

A

encode all auditory information and pass onto nerve fibres

have stereo cilia hair bundles arranged in size difference
mechanosensitive ion channels are at tips of short stereo cilia - connected to taller stereo cilia using tip links

rest:
tension
open channels = resting inward current carried by potassium (pos to neg inside cell)
potassium > large electrical gradient = large conc gradient for potassium exit

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42
Q

IHC - rest

A

Slight tension causes MET channels to be slightly open = inward current of K+ ions down an electrical gradient

Internal electrical charge is negative in IHC

Large concentration gradient for K+ causes slight depolarisation (MP becomes less negative to resting potential)

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43
Q

IHC - sound

A

excitatory phase push hair bundles towards stereo cilia, increasing the tension

larger MET current as more K+ flow

depolarisation of IHC - activates calcium and potassium channels

mature hair cells respond with graded receptor potentials

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44
Q

IHC - response to inhibitor phase of sound

A

deflect to shorter stereocilia

turns off MET current

hyper polarises below RP = little neuronal activity

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45
Q

IHC - response to sustained sound

A

afferent activity (cycles of depolarisation and hyperpolarisation)

hair bundles pushed back and forth

tight seperation between endolymph and perilymph = K+ enters down electrical gradient and leaves via chemical gradient

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46
Q

outer hair cells

A

shorten and lighten in time with frequency = electromobility

work as cochlear amplifier

V shaped hair bundle

voltage gated potassium channels

prestin molecule = allows electro mobility

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47
Q

OHC at rest

A

the same as IHC

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48
Q

positive feedback off OHCs

A

increase movement in basilar membrane
increase stimulation of IHC hair bundles
OHCs amplify stimulation of IHCs

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49
Q

OHC amplification of basilar membrane

A

OHC electromotility amplifies the basilar membrane motion over a narrow CF region

BM movement is greatly increased with cochlear improvement

results in highly tuned IHC

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50
Q

areas involved in ventral stream

A
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51
Q

columnar organisation (neurons organised into columns) of the cortex

A

ocular dominance - process visual info from one eye to the other

orientation - respond to horizontal or vertical stimuli

direction - process direction of motion stimuli

blobs - process colour, input from parvocellular cells

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52
Q

simple cells in V1

A

elongated receptive field
respond to bar shaped stimuli presented at specific orientation

located in layers 4 and 5 of V1

integrate inputs from multiple retinal ganglion cells

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53
Q

complex cells in V1

A

respond stimuli at different orientations

position invariance - respond to stimuli at any point of their receptive field

integrate inputs from multiple simple cells with overlapping receptive fields

layers 2,3,5

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54
Q

summary of receptive fields downstream of V1

A

increase in complexity and receptive field size

neurons in higher visual areas respond to more complex features

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55
Q

Jennifer aniston neuron

A

showed the existence of single neurons in the medial temporal lobe (MTL) that selectively respond to highly specific visual stimuli (e.g Jennifer Aniston)

showed hierarchical organisation

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56
Q

issues with discovery of Jennifer aniston neurons

A

poor in scale and orientation variance - may not respond to picture if at diff scale or orientation

study didn’t consider wider brain networks

relied on intracranial recordings - small amount of neurons and invasive

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57
Q

hierarchical model of object recognition

A

increases in stimulus complexity and receptive field size

  1. detection of edges
  2. detection of combination of edges and contours
  3. detection of object parts (e.g. face)
  4. detection of objects from one point of view
  5. view-invariant object detection (specific person)
  6. categorisation (a human)
58
Q

lateral geniculate nucleus

A

6 layers

relays information from retina to visual cortex (V1)

retinotopically organised - neurons receive input from adjacent regions in retina

receives input from magnocellular and parvocellular cells (retinal ganglion cells)

59
Q

areas involved in ventral stream

A

Visual cortex - V1
secondary visual cortex - V2
visual area - V4
inferior temporal cortex
fusiform face area - FFA

60
Q

retinotopic maps

A

representations of visual field in brain

organised based on spatial layout

61
Q

dorsal stream

A

primary visual cortex (V1)

middle temporal area

posterior parietal cortex

62
Q

superior colliculus

A

7 layers

regulates saccadic movements

receives input from ganglion cells in retina from different sensory modalities: somatosensory cortex and visual cortex

63
Q

direction selectivity

A

ability of neurons to respond selectively to motion in specific directions

64
Q

orienting reflex

A

automatic

orients sensory neurons towards stimulus

detects potential threats

65
Q

brain areas involved in orienting reflex

A

tectum (SUPERIOR COLLICULUS)

pretectum - relay station between retina and superior colliculus

hindbrain - medulla and pons

motor neurons

66
Q

direction-selective ganglion cells

A

input from bipolar cells = excitatory signals
inhibitory input from amacrine cells

asymmetric mix of excitatory and inhibitory inputs = allows preferential responses

67
Q

preferred direction for direction-selective cells

A

excitatory inputs are larger than inhibitory inputs = depolarisation and firing of the ganglion cell.

68
Q

null direction for direction-selective cells

A

inhibitory inputs are larger than excitatory inputs = hyperpolarisation and suppression of neuronal activity.

69
Q

declarative memory

A

conscious
encoded in symbols and language

70
Q

explicit v implicit memory

A

explicit = memory that can be consciously recalled

implicit = memory that cannot be consciously recalled

71
Q

habituation

A

decrease in response to a repeated, harmless situation

72
Q

3 types of memory in aplysia

A

habituation

sensitisation

associative learning (classical)

73
Q

cellular basis of habituation

A

occurs between sensory and motor neurone

reduction in transmitter release from sensory
due to depletion of readily releasable pool

74
Q

cellular basis of sensitisation

A

release of serotonin from L29 neuron

activates g-coupled protein receptors

increasing cAMP levels

activates protein kinase A, inactivates potassium channels

= long depolarisation and enhanced vesicular release

75
Q

sensitisation

A

organism enhances response to unpleasant stimulus due to presence of more intense stimulus

76
Q

associative learning

A

pairing neutral stimulus with aversive stimulus

calcium influx = enhanced synaptic transmission

77
Q

long term potentiation

A

synaptic strength is increased
increase in amplitude of excitatory post synaptic potentials

input specificity - only synapses with high frequency stimulation

78
Q

long term depression

A

synaptic strength decreased
decrease in EPSP

79
Q

mechanism of LTP - induction

A

postsynaptic NMDARs activated by glutamate (excitatory)

removal of magnesium block from depolarisation

calcium = signalling cascades
activates calmodulin kinase II, PSD protein (2-5%)

autophosphorylation triggered by calcium

Phosphorylation enhances AMPA currents

80
Q

mechanisms of LTD

A

low frequency stimulation

similar to LTP but phosphatases signalled by calcium = dephosphorylation

81
Q

hebbian synapse

A

coordinated activity between pre and post synaptic neurones strengthen synaptic communication

82
Q

hippocampal circuit

A

neural pathway involved in memory formation

Information > entorhinal cortex > dentate gyrus > CA3 via mossy fibers, followed by projections from CA3 to CA1 via Schaffer collaterals. Output from the hippocampus occurs via the fornix and subiculum

83
Q

glutamate receptors

A

primary excitatory neurotransmitter

acts on 3 receptors:
- NMDA - selective for calcium

  • non-NMDA (AMPA) - fast excitatory transmission, selective for sodium
  • metabotropic glutamate (mGlu)
84
Q

similarities between LTP and LTD

A

both depend on calcium signalling

85
Q

expression

A

dendritic spines and alterations in synaptic morphology

86
Q

trafficking of AMPARs

A

LTP -
more postsynaptic receptors
more excitatory postsynaptic currents = AMPAfication

LTD -
opposite

87
Q

cerebellum - LTD between parallel and purkinje cells

A

weaker but more connections than climbing fibres

climbing fibre input causes signalling cascade = weakens synapses causing LTD

88
Q

purkinje cells and climbing fibres

A

stronger but less synapses

activation of climbing fibres = glutamate

binds to ionotropic AMPARs and metabotropic glutamate receptors on postsynaptic membrane

activates phospholipase C into IP3 and DAG

releases calcium and DAG activates protein kinase C

phosphorylation of AMPA and endocytosis = LTD

89
Q

why are simple model systems (worms) used to study memory

A

simpler circuits - few neurones
less temperature sensitive and can create mutation genes

90
Q

detection of interaural level differences

A

difference in loudness
louder in ear closest to source

as small as 1-2 dB

loudness depends on how far away sound is from centreline

localises higher frequency sounds

91
Q

detection of interaural time differences

A

difference in arrival time of sound

2 microseconds

also depends on how far away from centreline

localises low frequency sound as longer wavelengths - time delay more detectable

92
Q

brain areas involved in sound localisation

A

cochlear nucleus
lateral superior olive
medial superior olives

93
Q

interaural level differences - lateral superior olive

A

LSO - excitatory input from ear nearest to sound (inhibitory from furthest ear)

simultaneous arrival = summation =LSO excitatory-inhibitory pathway

94
Q

ILD circuit function - left side of head

A

excitatory input larger than inhibitory
summation = excitatory

ILD is positive for left LSO

LSO output is maximal

95
Q

ILD circuit function - moving towards right ear

A

inhibitory input increases - ILD decreases

population output for LSO reduces

96
Q

ILD circuit function - centreline

A

ILD = 0 as inputs are equal

population output for LSO is half maximal

97
Q

ILD circuit function - closer to right ear

A

ILD becoming negative
inhibitory input larger

population output of LSO is low

98
Q

ILD circuit function - right ear

A

most negative for left LSO
ILD value = maximum

inhibitory output biggest

population output for LSO is very low

99
Q

how both LSOs work together:

A

each LSO receives excitatory input from near ear an inhibitory from far ear

outputs opposite but balanced

most overlap when in central region

100
Q

inter neural time differences - medial superior olives

A

two excitatory inputs converge in MSO

time difference = excitatory-excitatory pathway

101
Q

ITD circuit function - left side of head

A

sound reaches far ear after maximal delay - travel further

NO summation + largest delay

overall population output of MSO = minimal

102
Q

ITD circuit function - moving towards right ear

A

less delay

probability of simultaneous arrival increases

population output of Mao increases

103
Q

ITD circuit function - centreline

A

ITD = 0

still a delay

population output of MSO = half maximal

104
Q

how do senses interact

A

initial circuits formed, calibrated using alignment with visual map.
auditory map refined to overlay visual map

auditory map - adaptive plasticity

105
Q

ITD circuit function - closer to right ear

A

small delay
probability of simultaneous excitation increases

population out of MSO = large

106
Q

barn owls - how do senses interact study

A

visual field artificially shifted - dark chamber
head angle relative to stimulus recorded

after 42 days:
visual response shifted to visual stimulus
auditory response shifted to align with modified visual field

after removal:
visual re-aligns, auditory remains shifted

107
Q

ITD circuit function = right ear

A

inputs arrive at same time
probability of simultaneous arrival - highest

population output of left MSO maximal for sound at right ear

108
Q

how both MSOs work together:

A

population outputs are opposite but balanced
output highest with sound from opposite side of head

most overlap at centre

109
Q

comparison of ILD and ITD

A

ILD - lateral superior olives
ITD - medial superior olives

Left LSO = sound from left
Left MSO = sound from right

110
Q

olfactory sensory neurons

A

as they mature, they narrow so they express a single olfactory receptor each

neurons expressing the same receptor converge on the same glomerulus = odour specificity

when molecule binds to receptor, G-protein is activated = action potentials

111
Q

key brain areas - smell/taste information

A

human:
olfactory bulb (antennal lobe)
piriform cortex
amygdala

taste circuits:
solitary nucleus of brainstem
ventral posterior medial nucleus of thalamus
insula and parietal cortex

insect:
mushroom body (Kenyon cells) - learned behaviour
lateral horn - innate behaviour - if silenced, don’t distinguish between odours

112
Q

findings from barn owl study

A

auditory space map is modified based on changes to visual map

= visual map dominant for space perception
and auditory map takes longer to readjust

113
Q

labelled line vs combinatorial code

A

LL = method of coding a stimulus that has a direct pathway from neuron to stimulus

CC = many neurons may respond to a stimulus

114
Q

signal transduction

A

can amplify weak signal through signal transduction cascade

e.g. enzymes can make many cAMP which activates channel letting more in

115
Q

lateral inhibiton

A

activity of one neuron supresses activity of neighbouring neurons

improves discrimination

116
Q

olfaction - stimulus dimensionality

A

multi-dimensional chemical space rather than sound and light

117
Q

ensuring odour specificity

A

receptor-specific matching of sensory neurons to second-order neurons

118
Q

drosophila v mammals

A

olfactory receptor neurones v olfactory sensory neurones

projection neurones v mitral cells, tufted cells

119
Q

first relay synapse taste/smell

A

transforms odour code
reduces noise
strengthens weak responses

120
Q

decorrelation

A

Ensuring that responses to different stimuli are distinct, even if they activate overlapping populations of sensory neurons.

121
Q

gaining control

A

sensitive to both strong and weak odours

122
Q

different key computations - olfactory/gustatory processing centres

A

dense codes = innate behaviours
sparse codes = learning

gustatory = temporal coding

123
Q

classsical conditioning in drosophila

A

CS such as odour paired with US like electric shock

124
Q

biased random walk

A

bacteria can swim straight or turn (tumble)
worse = new direction to head towards good odour

c.elegans use same rule - if odour is increasing, suppress turning by silencing inhibitory interneuron

125
Q

Kenyon cells

A

mushroom body

receive input from projection neurons
integrate with dopaminergic neurons

sample small regions in projection neuron coding space = turns dense code into selective code

126
Q

MBONs - mushroom body output neurons

A

mushroom body

relay processed olfactory info to brain

receive input from Kenyon cells and DANs

project axons

approach or avoidance behaviour

127
Q

dopaminergic neurons (DANs)

A

release dopamine

signal wether odour is associated with reward or punishment

project axons, form synapses with Kenyon cells
tile in one-to-one matching so each compartment of mushroom body receives input from a specific subset of DANs

128
Q

overview of olfactory associative memory

A

odour > olfactory receptor neurons > Kenyon cells

reward or punishment (dopaminergic neurons) > behavioural output

if too many Kenyon cells active for odour = overlap between which Kenyon cells respond

129
Q

neural circuitry underlying olfactory learning

A

when odour is paired with reward (sugar)
DANs suppress synapses between Kenyon cells and MBONs that lead to avoidance = LTD
= strengths connections associated with approach

130
Q

GAL4 split system

A

GAL4 = transcription factor binding to DNA

divide into two segments (activation domain, dNA binding domain) with two zipper domains (allows interaction)

half of GAL4 placed under control of one enhancer while the other placed under control of the other

when both halves expressed in same cells, they activate functional GAL4 = activation of genes

131
Q

flies learn backwards if shock precedes odour

A

they smell the odour when shock finished = relief from pain

US (shock) before CS (odour) = approach
CS before US = avoid

132
Q

forward and backward pairing

A

forward = Kenyon then dopamine = depress KC-MBON synapses. - CONDITIONED AVOIDANCE

backward = dopamine (reward) then Kenyon = potential KC-MBON synapses

133
Q

Kenyon cells - 2 dopamine receptors

A

DopR1 = learning
uses forward pairing (depression)
DAN after KC signal = cAMP prodcution is symmetric

Gs pathway - andenylyl cyclase - ATP > cAMP

DopR2 = forgetting
backward pairing (potentiation)
Gq activates PLC = IP3 release Ca2+

DAN before KC = increase cMAP and Ca

134
Q

mitral cells grow dendrites in multiple glomeruli (mutation in mice)
OR blocking local inhibitory neurons

A

cant discriminate odours
may be sensitive to low odours

135
Q

similarities between mushroom body and cerebellum

A

hierarchical organisation

projection neurons are mossy fibres in cerebellum that synapse onto granule cells (form on parallel fibres like in mushroom body)

circuit allows for fish to learn to ignore wrong signals (electroreceptors) - synaptic depression to cancel out incorrect signals

136
Q

calcium and IP3

A

if calcium binds to receptor first = IP3 cannot bind (locks)

137
Q

drift diffusion model

A

start at neutral level
sensory information pushes one way or another

drift rate = rate at which the decision variable accumulates evidence over time (Higher = faster decision-making)

138
Q

relationship between reaction time and rate of evidence accumulation

A

inversely proportional
faster evidence = shorter RT

139
Q

speed accuracy trade-off

A

when time frame for making decision is limited, accuracy is sacrificed for speed

140
Q

drosophila - reaction times

A

slowing down rate of accumulating evidence delays membrane potential and spiking threshold (Time to make decision) (slowed down by FoxP mutant)