neural circuits Flashcards
glutamate
excitatory neurotransmitter - promotes AP
binds to NMDA and AMPA receptors
glutamate receptors
ionotropic - AMPA, NMDA - ion channels, rapid changes in membrane potential
metabotropic - activate intracellular cascades, neuronal excitability and synaptic transmission
the nervous system
detects change, recognises change, executes specific behavioural problem
patch clamp methods
pipette based: high contact between electrode and cell - cell-attached recording method
planar: whole cell, no electrode, grow cell into hole
configurations of patch-clamp
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
problem with patch clamp methods
cannot label many cells
limited ability to label specific cell type and live labelling
epifluorescent microscopes
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
difference between patch clamp and sharp electrode recordings
patch clamp = higher sensitivity of individual cells, higher spatial resolution
GFP
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
principles of GCAMP
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
how does GCaMP indicate changes in intracellular calcium levels
changes fluorescence in response to calcium binding
neurons brighter when calcium levels rise
benefit of using confocal microscope
better resolution in z axis
uses pinhole to eliminate out-of-focus light
scans across specimen in a raster pattern
3D data sets
channelrhodopsin
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
halorhodopsin
stimulated by yellow light
transmits chloride (hyperpolarisation)
inhibits neuronal activity and making the neuron more negative than resting potential
cajal and Golgi dye
cajal = fine details of dendritic trees
Golgi dye = labels neurons sparsely
issues of enhancer traps
cannot stain individual neurons
cant combine morphological and electrophysiologicology of same cell
sharp electrode recordings
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
visual system - 3 types of stimuli
food
predator
mate
two main pathways of visual system
ventral (information) - from V1 to temporal lobe
dorsal (localisation) - from V1 to parietal lobe
lateral geniculate nucleus
thalamus
relays information from retinal ganglion cells via optic nerve and tract to V1 cortex
layers = magnocellular (light), parvocellular (colour, fine detail), koniocellular
retina components
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
feedforward neurons
photoreceptors (rods (dim) and cones (bright))
bipolar cells (glutamatergic so release glutamate)
ganglion cells (output cells)
feedback neurons
horizontal (inhibitory)
amacrine cells
layout of retina
3 layers of neurons
2 layers of synapses
photoreceptor layer (outer nuclear layer)
inner nuclear layer - bipolar, horizontal, ganglion
ganglion cell layer
on cells
light = less glutamate into bipolar cells
depolarise
ON bipolar cells depolarise activating ON ganglion cells
centre surround organisation
off cells
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
inner plexiform layer
layer of synapses
four synapses between bipolar, amacrine and ganglion cells
receptive field
area of retina when illuminated activates a visual neuron
centre-surround organisation
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
types of ganglion cell
parvocellular - small dendritic trees and small receptive field with centre surround organisation
magnocellular - larger receptive field and dendritic trees, reacts to different colours
rods
activated by dim light
more cyclic GMP
cones
activated by bright light
phototransduction
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
important features of sound
encodes:
sound frequency - cycles per second (10(3))
sound intensity - range = 10(12)
onset - helps localise
duration
3 chambers of cochlea
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
organ of corti
sensory hair cells
connections frome nerve fibres to auditory nerve
on basilar membrane
hair cell resting gradient
-60mV
electrical gradient of 140mV between scala media and hair cells (vital for function)
how sound stimulates sensory hair cells
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
lower vs high frequency sound
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)
place frequency code
brain interprets position of active inner hair cell as a specific sound frequency
Neural firing rate used to encode sound intensity
inner hair cells
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
IHC - rest
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)
IHC - sound
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
IHC - response to inhibitor phase of sound
deflect to shorter stereocilia
turns off MET current
hyper polarises below RP = little neuronal activity
IHC - response to sustained sound
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
outer hair cells
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
OHC at rest
the same as IHC
positive feedback off OHCs
increase movement in basilar membrane
increase stimulation of IHC hair bundles
OHCs amplify stimulation of IHCs
OHC amplification of basilar membrane
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
areas involved in ventral stream
columnar organisation (neurons organised into columns) of the cortex
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
simple cells in V1
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
complex cells in V1
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
summary of receptive fields downstream of V1
increase in complexity and receptive field size
neurons in higher visual areas respond to more complex features
Jennifer aniston neuron
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
issues with discovery of Jennifer aniston neurons
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
hierarchical model of object recognition
increases in stimulus complexity and receptive field size
- detection of edges
- detection of combination of edges and contours
- detection of object parts (e.g. face)
- detection of objects from one point of view
- view-invariant object detection (specific person)
- categorisation (a human)
lateral geniculate nucleus
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)
areas involved in ventral stream
Visual cortex - V1
secondary visual cortex - V2
visual area - V4
inferior temporal cortex
fusiform face area - FFA
retinotopic maps
representations of visual field in brain
organised based on spatial layout
dorsal stream
primary visual cortex (V1)
middle temporal area
posterior parietal cortex
superior colliculus
7 layers
regulates saccadic movements
receives input from ganglion cells in retina from different sensory modalities: somatosensory cortex and visual cortex
direction selectivity
ability of neurons to respond selectively to motion in specific directions
orienting reflex
automatic
orients sensory neurons towards stimulus
detects potential threats
brain areas involved in orienting reflex
tectum (SUPERIOR COLLICULUS)
pretectum - relay station between retina and superior colliculus
hindbrain - medulla and pons
motor neurons
direction-selective ganglion cells
input from bipolar cells = excitatory signals
inhibitory input from amacrine cells
asymmetric mix of excitatory and inhibitory inputs = allows preferential responses
preferred direction for direction-selective cells
excitatory inputs are larger than inhibitory inputs = depolarisation and firing of the ganglion cell.
null direction for direction-selective cells
inhibitory inputs are larger than excitatory inputs = hyperpolarisation and suppression of neuronal activity.
declarative memory
conscious
encoded in symbols and language
explicit v implicit memory
explicit = memory that can be consciously recalled
implicit = memory that cannot be consciously recalled
habituation
decrease in response to a repeated, harmless situation
3 types of memory in aplysia
habituation
sensitisation
associative learning (classical)
cellular basis of habituation
occurs between sensory and motor neurone
reduction in transmitter release from sensory
due to depletion of readily releasable pool
cellular basis of sensitisation
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
sensitisation
organism enhances response to unpleasant stimulus due to presence of more intense stimulus
associative learning
pairing neutral stimulus with aversive stimulus
calcium influx = enhanced synaptic transmission
long term potentiation
synaptic strength is increased
increase in amplitude of excitatory post synaptic potentials
input specificity - only synapses with high frequency stimulation
long term depression
synaptic strength decreased
decrease in EPSP
mechanism of LTP - induction
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
mechanisms of LTD
low frequency stimulation
similar to LTP but phosphatases signalled by calcium = dephosphorylation
hebbian synapse
coordinated activity between pre and post synaptic neurones strengthen synaptic communication
hippocampal circuit
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
glutamate receptors
primary excitatory neurotransmitter
acts on 3 receptors:
- NMDA - selective for calcium
- non-NMDA (AMPA) - fast excitatory transmission, selective for sodium
- metabotropic glutamate (mGlu)
similarities between LTP and LTD
both depend on calcium signalling
expression
dendritic spines and alterations in synaptic morphology
trafficking of AMPARs
LTP -
more postsynaptic receptors
more excitatory postsynaptic currents = AMPAfication
LTD -
opposite
cerebellum - LTD between parallel and purkinje cells
weaker but more connections than climbing fibres
climbing fibre input causes signalling cascade = weakens synapses causing LTD
purkinje cells and climbing fibres
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
why are simple model systems (worms) used to study memory
simpler circuits - few neurones
less temperature sensitive and can create mutation genes
detection of interaural level differences
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
detection of interaural time differences
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
brain areas involved in sound localisation
cochlear nucleus
lateral superior olive
medial superior olives
interaural level differences - lateral superior olive
LSO - excitatory input from ear nearest to sound (inhibitory from furthest ear)
simultaneous arrival = summation =LSO excitatory-inhibitory pathway
ILD circuit function - left side of head
excitatory input larger than inhibitory
summation = excitatory
ILD is positive for left LSO
LSO output is maximal
ILD circuit function - moving towards right ear
inhibitory input increases - ILD decreases
population output for LSO reduces
ILD circuit function - centreline
ILD = 0 as inputs are equal
population output for LSO is half maximal
ILD circuit function - closer to right ear
ILD becoming negative
inhibitory input larger
population output of LSO is low
ILD circuit function - right ear
most negative for left LSO
ILD value = maximum
inhibitory output biggest
population output for LSO is very low
how both LSOs work together:
each LSO receives excitatory input from near ear an inhibitory from far ear
outputs opposite but balanced
most overlap when in central region
inter neural time differences - medial superior olives
two excitatory inputs converge in MSO
time difference = excitatory-excitatory pathway
ITD circuit function - left side of head
sound reaches far ear after maximal delay - travel further
NO summation + largest delay
overall population output of MSO = minimal
ITD circuit function - moving towards right ear
less delay
probability of simultaneous arrival increases
population output of Mao increases
ITD circuit function - centreline
ITD = 0
still a delay
population output of MSO = half maximal
how do senses interact
initial circuits formed, calibrated using alignment with visual map.
auditory map refined to overlay visual map
auditory map - adaptive plasticity
ITD circuit function - closer to right ear
small delay
probability of simultaneous excitation increases
population out of MSO = large
barn owls - how do senses interact study
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
ITD circuit function = right ear
inputs arrive at same time
probability of simultaneous arrival - highest
population output of left MSO maximal for sound at right ear
how both MSOs work together:
population outputs are opposite but balanced
output highest with sound from opposite side of head
most overlap at centre
comparison of ILD and ITD
ILD - lateral superior olives
ITD - medial superior olives
Left LSO = sound from left
Left MSO = sound from right
olfactory sensory neurons
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
key brain areas - smell/taste information
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
findings from barn owl study
auditory space map is modified based on changes to visual map
= visual map dominant for space perception
and auditory map takes longer to readjust
labelled line vs combinatorial code
LL = method of coding a stimulus that has a direct pathway from neuron to stimulus
CC = many neurons may respond to a stimulus
signal transduction
can amplify weak signal through signal transduction cascade
e.g. enzymes can make many cAMP which activates channel letting more in
lateral inhibiton
activity of one neuron supresses activity of neighbouring neurons
improves discrimination
olfaction - stimulus dimensionality
multi-dimensional chemical space rather than sound and light
ensuring odour specificity
receptor-specific matching of sensory neurons to second-order neurons
drosophila v mammals
olfactory receptor neurones v olfactory sensory neurones
projection neurones v mitral cells, tufted cells
first relay synapse taste/smell
transforms odour code
reduces noise
strengthens weak responses
decorrelation
Ensuring that responses to different stimuli are distinct, even if they activate overlapping populations of sensory neurons.
gaining control
sensitive to both strong and weak odours
different key computations - olfactory/gustatory processing centres
dense codes = innate behaviours
sparse codes = learning
gustatory = temporal coding
classsical conditioning in drosophila
CS such as odour paired with US like electric shock
biased random walk
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
Kenyon cells
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
MBONs - mushroom body output neurons
mushroom body
relay processed olfactory info to brain
receive input from Kenyon cells and DANs
project axons
approach or avoidance behaviour
dopaminergic neurons (DANs)
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
overview of olfactory associative memory
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
neural circuitry underlying olfactory learning
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
GAL4 split system
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
flies learn backwards if shock precedes odour
they smell the odour when shock finished = relief from pain
US (shock) before CS (odour) = approach
CS before US = avoid
forward and backward pairing
forward = Kenyon then dopamine = depress KC-MBON synapses. - CONDITIONED AVOIDANCE
backward = dopamine (reward) then Kenyon = potential KC-MBON synapses
Kenyon cells - 2 dopamine receptors
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
mitral cells grow dendrites in multiple glomeruli (mutation in mice)
OR blocking local inhibitory neurons
cant discriminate odours
may be sensitive to low odours
similarities between mushroom body and cerebellum
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
calcium and IP3
if calcium binds to receptor first = IP3 cannot bind (locks)
drift diffusion model
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)
relationship between reaction time and rate of evidence accumulation
inversely proportional
faster evidence = shorter RT
speed accuracy trade-off
when time frame for making decision is limited, accuracy is sacrificed for speed
drosophila - reaction times
slowing down rate of accumulating evidence delays membrane potential and spiking threshold (Time to make decision) (slowed down by FoxP mutant)
