Neuronal Networks Flashcards
Connectomics
study of the brain’s structural and functional connections between cells
Allen Brain Atlas
Brain maps of gene expression in human and mouse brains
serves as dataset for further research to compare
10,000 different brain cell types
Neuronal complexity
complexity is related to the requirements of the organism
Caenorhabditis elegans
Transparent nematode
unsegmented pseudocoelomate and lacks respiratory or circulatory systems
302 neurons
basic organism + behaviours e.g. chemo/thermotaxis and mechanotransduction
Vision in forager ants
Detect polarised light to find their way home
Rhabdomeric receptors
contains visual pigment
structure is tubules of rolled up membrane (microvilli)
upward dorsal rim receptors match w celestial e-vector pattern
ocelli
small eyes next to apposition eyes that detect polarised light
apposition compound eyes
type of compound eye found in ants
ommatidia
unit of compound eye
e-vector
electrical/euclidean vector
Polarised light
light waves in which the vibrations occur in a single plane
Sherrington study 1950s
It was the introduction of electron
microscopy that led to two groups
describing the anatomical basis of synapses
in the mid-1950s
Both groups described the small vesicles
close to the broadening of the presynaptic
element 20–60 nm in diameter and the
extracellular space between the two
swollen membranes of some 20 nm
Katz et al. 1960s
experiment of neurotransmitter presence in synapse as form of transmission
miledi used tetrodoxin to stop APs on either side of synapse
still a response(small) - release of transmitter
Steps of chemical synaptic transmission
- AP initiation
- Depolarisation of terminal
- Fusion of vesicles to membrane
- Diffusion
- Binding to receptors
role of calcium in vesicle fusion
When an action potential reaches the presynaptic terminal, voltage-gated calcium channels on the plasma membrane of the terminal open, allowing calcium ions to flow into the cell. This influx of calcium triggers a series of events that ultimately leads to the fusion of synaptic vesicles with the plasma membrane, releasing their contents into the synaptic cleft.
Specifically, calcium ions bind to a protein called synaptotagmin, which is located on the surface of the synaptic vesicle. This binding causes synaptotagmin to undergo a conformational change, which in turn triggers the recruitment of other proteins involved in the fusion process, such as SNAP-25 and synaptobrevin. These proteins work together to form a complex that brings the synaptic vesicle into close proximity with the plasma membrane, leading to the fusion of the vesicle with the membrane and the release of neurotransmitters into the synaptic cleft.
astrocyte
type of glial cell
wrap around synapse to limit outer diffusion
containers transporters to clear neurotransmitters e.g. glutamate, GABA
Contain glucose/glycogen to fuel neurons in shortages
synaptic modulation
long term potentiation
a process involving persistent strengthening of synapses that leads to a long-lasting increase in signal transmission between neurons
release probability
low and high release probability synapses
more VDCCs = higher probability
kiss and run model
More likely to be involved in neurotransmitter transmission
Partially empty vesibles present in EM
Porosomes present in synaptic bulbs
full fusion collapse model
complete fusion/collapse into membrane
slow dilation possibly for small molecules to be released quickly
Thoreson et al. (salamander photoreceptors)
Larger fusion pores - for bigger molecules/peptides
Diffusion equation
t = (Δx^2)/2D
t = diffusion time
x = distance across the cleft
D = diffusion coefficient for the transmitter
Porosomes
Permanent structures that act as a dock for transient vesicles
SNARE proteins involved
SNAREs
Proteins involved with membrane fusion at neural synapses
t and v SNARE complexes work together
Synaptic conductance (Gsyn)
The degree to which the synapse conducts electricity, calculated as the ratio of the current which flows to the potential difference present
Determined by 3 things: Number of channels(Nc), Single channel conductance(g), open probability (Popen)
Gsyn = g(Nc x Popen)
Duration of Gsyn determined by?
Transmitter profile - how long transmitter stays in cleft
Channel Kinetics
SM proteins
Work with SNARE to promote membrane fusion
Coagonist of SNARE
Sec1/Munc18 protein
Excitatory post-synaptic potentials
- Makes it more likely to fire an AP
- temporary depolarisation of postsynaptic membrane
- flow of positive ions into cell
- ligand gated ion channels responsible for this
Inhibitory post-synaptic potentials
- Makes it less likely for AP to fire
- inhibitory neurotransmitters bind to postsynpatic membrane
- induced change in permeability
- flow of negative ions into cell/positive ions out
- negative potential increasess = closer to HYPERPOLARISATION
Spatial Summation
Spatial summation, on the other hand, is a process by which the strength of a signal is enhanced by the combined activity of multiple neurons that are spatially close to each other. In the context of brain waves, spatial summation refers to the phenomenon where the amplitude or power of a brain wave is increased by the simultaneous activity of multiple neuronal populations that are spatially close to each other.
Glutamate
Main excitatory neurotransmitter
Dianion amino acid
2 types of receptors: Ionotropic and metabotropic
Ionotropic: AMPA, NMDA, Delta and Kainate
Metabotropic: Groups 1,2 and 3 e.g mGlur
Ionotropic receptors
Ligand gated ion channels
Open to allow ions such as sodium, potassium and calcium
Specialised for fast excitation
Metabotropic
Second messneger system
Slow, sustained excitatory response
G-protein couple receptors
they are involved in learning, memory, anxiety, and the perception of pain. They are found in pre- and postsynaptic neurons in synapses of the hippocampus, cerebellum and the cerebral cortex
NMDA receptor
NMDA is its agonist
Blocked by Mg2+ and Zn2+ ions
Glutamate binding receptor
Heterotetramer
Activation of NMDA receptors results in the opening of the ion channel that is nonselective to cations
NMDARs require the binding of two molecules of glutamate or aspartate and two of glycine
More permeable to Ca2+ to cause activation of genes
AMPA receptor
Tetramer with each subunit having a binding site for glutamate
Opens to allow cations through when activated
Kainate receptor
Heterotetramer
Permeable to sodium and potassium ions
Slight permeability to Ca2+
Metabotropic (G-protein cascades) and ionotropic
Agonist
Compound that can bind to and cause activation of a receptor, thus mimicking an endogenous ligand or neurotransmitter
GABA
Main inhibitory neurotransmitter
gamma-aminobutyric acid
Synthesised by precursor glutamate
GABA receptors
GABAA in which the receptor is part of a ligand-gated ion channel complex - allow flow of chloride ions into cell e.g. alpha, beta, gamma, delta, pi, rho and theta subunits
GABAB metabotropic receptors, which are G protein-coupled receptors that open or close ion channels via intermediaries (G proteins) e.g. GABABR1/2 subunits
GABAergic neurons
Neurons that produce GABA as their output
GABA in immature and mature neurons
Depolarises immature neurons as 2Cl- in and 1Cl- out with sodium and potassium being let in as well
Inhibits mature neurons by maintaining Cl- concentration at equilibrium - therefore can’t depolarise
Close to hyperpolarisation but doesn’t quite get there
DEVELOPMENTALLY REGULATED
Cl- can alter day night cycle in certain nuclei
Benzodiazapines
benzodiazepine binding acts as a positive allosteric modulator by increasing the total conduction of chloride ions across the neuronal cell membrane when GABA is already bound to its receptor. This increased chloride ion influx hyperpolarizes the neuron’s membrane potential.
Types of basic network motifs
Feedforward
Feedback
Disinhibition
Cerebellum
Made up of orderly repeating microcircuits
Geometric array
Involved in sensory motor control + eyes
Purkinje cells
Soma diameter 50-80 μm
1 -2 primary dendrites, but hundreds of
secondary and tertiary branches.
100-300,000 granule cell axons synapse
onto a single Purkinje cell.
Granule cells
Soma diameter ~10 μm
3 – 4 dendrites. Each only ~15 μm in length
Each granule cell sends a single axon into the
Purkinje cell dendritic tree.
Parallel fibres
Granule cell axons
Mossy fibres
Basket cells
Stellate cells
Golgi cells
Soma diameter ~30 μm
Ascending dendrites branch within the
molecular layer and the axonal plexus
arborists within the granule cell layer. Each
Golgi cell inhibits thousands of granule cells.
alpha6 beta2 delta GABAA receptors
Only found outside of synapses
Delta has a higher affinity for GABA
Resting ambient [GABA] by having an equilibrium w GABA transporters
Generates tonic conductance
Tonic conductance
Tonic conductance refers to the baseline level of ion conductance through the cell membrane of a neuron or other electrically excitable cell. It is the level of ion flow that exists in the absence of any external stimuli or synaptic input
Glomerular synapse in cerebellum
Brainbow study
Why is dense and strong coding of mf inputs most likely in the cerebellum?
The arrangement favours robust receptive fireld mapping
Why is dense and strong coding of mf inputs most likely in the cerebellum?
The arrangement favours robust receptive fireld mapping
Mindscope
Attempting to understand the computations that lead from photons to
behaviour by observing and modelling the physical transformations of signals in the visual
brain of behaving mice for one perception-action cycle
aims to catalogue all the building blocks (over 100 distinct cell types) of the
mouse visual system (e.g. neurons of the retina, thalamus, colliculus, cortex) and model
their dynamics.
Split/binocular vision
Split vision, also known as binocular vision, is a type of vision where an organism’s eyes are positioned in a way that allows them to see two different images simultaneously, which are then fused together by the brain to create a single three-dimensional image.
How long does it take for visual inputs to be processed by our brains?
0.25s
What is the order of cells that light passes through in the retina?
Photoreceptors > horizontal + bipolar > amacrine > ganglia
Ganglion cell
Rod cells
Photoreceptor cells responsible for vision in low light (work best in low)
Optimized for detecting changes in light intensity over a wide range of levels.
More sensitive to light than rod cells
Cone cells
3 opsin types - S, M, and L –> trichromatic
Densely packed in fovea
Work best in bright light
Response time to stimuli faster than rod cells
Rhodopsin(OPN2)
Opsin + retinal attached
lines membrane shelves in rod cells
What neurotransmitter do photoreceptor cells release?
Glutamate to inhibit bipolar cells and
OPN1LW
Long Wavelength Sensitive Opsin
λmax in the red region (564 nm) of the electromagnetic
spectrum. Despite its name, this receptor has a secondary
response in the violet high frequencies.
OPN1MW
Middle Wavelength Sensitive Opsin
λmax in the green region (534 nm).
OPN1SW
Short Wavelength Sensitive Opsin
λmax in the blue region (420 nm).
Melanopsin (OPN4)
λmax in the blue region (488 nm) but broader then the other
opsins. This opsin is found in ipRGCs and mediates
circadian rhythms and pupillary reflex but is not involved in
image-forming.
ipRGC
intrinsically photosensitive retinal
ganglion cells
found in inner plexiform layer
tetradodoxin
sodium channel blocker
inhibits APs
rod amacrine cell
Inhibitory interneuron
Lateral inhibition
Can be GABAergic or Glutaminergic
what neurotransmitter do OFF Bipolar cells release in the retina?
Dopamine
what neurotransmitter do ON Bipolar cells release in the retina?
Glutamate
Function of horizontal cells
Lateral inhibition between adjacent photoreceptors
Lateral inhibition helps to sharpen the contrast and enhance the spatial resolution of visual information transmitted to the brain.
Centre-surround receptive field
Allows ganglion cells to transmit information not merely about whether photoreceptor cells are exposed to light, but also about the differences in firing rates of cells in the center and surround. This allows them to transmit information about contrast.
Central excitatory region + inhibitory surround region
Size of receptive field
density of photoreceptors
Spatial frequency
The number of cycles of a visual pattern that occur within a given unit of visual space.
A cycle refers to a complete repetition of the visual pattern, such as a sine wave or a bar.
Small receptive fields
high spatial frequencies, fine detail.
Large receptive fields
Low spatial frequencies, coarse detail
What are the 3 thalamic regions that receive retinal input?
dorsal lateral geniculate nucleus (dLGN)
ventral lateral geniculate nucleus (vLGN)
& intergeniculate leaflet (IGL)
dLGN
Primary visual relay – involved in
conscious visual processing
IGL
Input from melanopsincontaining
retinal ganglion cells – role in
circadian rhythm generation
vLGN
Integration of sensorimotor
information
Types of memory
Explicit
Procedural
Sensory
Short-term
Long-term
Procedural/Implicit memory
Memories that dont directly involve consciousness such as physical actions and skills
Model of synaptic plasticity
Donald Hebb 1949
Strength of connections change during learning and memory
Long term potentiation
When a synapse is repeatedly activated
this increases efficiency of synaptic transmission
connections between neurons enhanced
LTP at molecular level
Changes in number of channels at synapses and volume of neurotransmitter released
Hebb’s postulates
Hebbian learning
Cell assembly
Phase sequence
Hebbian learning
Connections between neurons increase in efficacy in proportion to the degree of correlation between pre and post-synaptic activity
Cell assembly
Group of neurons that will tend to fire together
Phase sequence
Thinking is the sequential activation of
sets of cell-assemblies.
