Neuronal complexity Flashcards
why are complex circuits formed?
one neurone can have 1000s of inputs and synapse onto a vast no. of other cells
what are the 5 aspects of synaptic modulation?
complex forms of synaptic activity
facilitation, depression + temporary potentiation
Hebbian synapse
long term protection
synaptic plasticity
what is facilitation?
in the long term, what to frequently used pathways become?
when 2 or more Abs reach the presynaptic terminals in a short period of time
-> more NT is released per AP
= stronger response in the postsynaptic neurone
more effective pathways
how does the interval between spikes effect facilitation?
the smaller the interval between spikes
-> the greater the facilitation
what is a tetanic train?
a rapid succession of APs
what is depression?
- tetanic train causes depletion in NT
- decreased NT release
- decreased EPSP
= depression
how can a synapse recover from depression?
post-tetanic potentiation
= increase in synaptic vesicles available per incoming AP
-> short term enhancement of synapse’s activity
what are the 2 presynaptic parameters that influence short-term plasticity?
local intracellular Ca2+ conc and Ca2+ binding protein conc
readily-resealable pool of vesicles
short term plasticity is specific for?
individual synapses
- even if its in the same axon
same activity in same neurone
-> could cause depression in one synapse and facilitation in another
how does post-tetanic potentiation represent an elementary form of memory?
a high rate of stimulation in the presynaptic neurone
-> leads to a gradual increase in amplitude of postsynaptic potential
= represent storage of information about a previous activity
what did Hebb hypothesise?
what does this mean?
a form of co-ordinated activity for a series of neurones connected together that would strengthen specific pathways
- pathways respond better to particular stimuli
- pathways would become dedicated to 1 kind of remembered event
- a neurone may have several inputs
in a Hebbian synapse, what effects may several inputs have on a neurone?
inputs that operate similarly work in harmony
-> strengthens post-synaptic response
= increases efficiency of connections
-> greater post-synaptic response
inputs not working in the same way will be weakened
which receptors have been associated with synapses that can learn?
NMDA receptors
what is long term potentiation?
neurones responding to a particular kind of stimulation
-> resulting in enhanced synaptic activity
what is involved in LTP formation?
what factors are also involved in this process?
activation of NMDA receptors
changes in in the behaviour of calcium/calmodulin-dependent kinases
retrograde acting factors
= those that effect the presynaptic neurone behaviour
what is long term depression?
what can cause it?
decreased response to particular inputs
if high activity in the synapse requires high conc of calcium in the presynaptic component
what are all forms of memory believed to be due to?
which parts of the brain demonstrate this?
LTP
Hippocampus (spatial memory)
Amygdala (fear)
Cortex (motor skill)
describe the structure of a rodent hippocampus
- perforant path carries input to granule cell in Dentate gyrus
- granule cell sends out an axon to a pyramidal cell in CA3
- this sends out an axon to another pyramidal cell in CA1
what are the 3 principle pathways in a rodent hippocampus?
- Perforant
- entorhinal cortex to DG
- granule cells - Mossy fibre
- DG to CA3
- pyramidal cells - Schaffer collateral
- CA3 to CA1
- pyramidal cells
how can activity of LTP of Schaffer collateral- CA1 synapses be measured?
apply tetanus to pathway 1 in axon of CA3 pyramidal cells
measure the post-synaptic activity of the different pathways in CA1 pyramidal cell before and after tetanus
look at whether there’s a change between before and after
- if there’s no difference in pathway 2
= no LTP induced
what happens after LTP?
EPSCs (=currents) are increased
what are the pre and post synaptic mechanisms of LTP?
pre
= increase in probability of NT release
-> amount of quanta released increases
post
= changes in production of proteins involved in the synapse
-> due to AMPA receptor (glutamate receptor)
how does LTP affect kinases?
CaMKII
- normally calcium-calmodulin dependent
- now autophosphorylated form active without Ca2+
PKC and PKA activity effected too
what is AMPA?
what are the changes in AMPA receptors?
an agonist for glutamate
activation of NMDA receptors
- > increase in density of AMPA receptors on PS membrane
- > increase in sensitivity of PS cell
how are silent synapses converted into active synapses via AMPAR insertion?
- remove blockage that prevents NMDAR activation
- Ca2+ enters via NMDARs
- alters activity of Ca-CaM II
- alters protein synthesis
- > inclusion of AMPA receptors into PS membrane
why are NMDAR the most important aspect of considering how LTP occurs?
they lead to a change in protein synthesis
= long term change
describe how NMDAR is activated
- glutamate or NDMA binds to agonist binding site
- glycine (co-agonist) binds to allosteric site
- independent depolarisation of membrane
- > removes Mg2+ block - Ca2+ and Na+ ions flow through
what are the other regulatory regions of NMDAR?
endogenous polyamines
- low microM potentiates
- high microM inhibits
phosphorylation site
redox site
- reducing agents potentiate
- oxidation reduces NMDAR activation
describe NDMAR structure
how is NMDAR effected by its subunits?
(at least)
2 x NR1
2 x NR2
variability in the types of NR subunits
-> impacts variability in NMDAR
what are retrograde messengers?
give 3 examples
messengers released by the post-synaptic cell that modify the response of the pre-synaptic cell
- > modified quantal release
- > impacts how NMDAR respond + how AMPAR are incorporated in the synapse
nitric oxide
carbon monoxide
arachidonic acid
