Synaptic Plasticity Flashcards
Santiago ramón y Cajal (1894) stated
memories might be formed by strengthening connections between neurons
Hebbs law =
when axon A is near enough to excite cell B and repeatedly takes part in firing it - some growth process or metabolic change takes place in one or both cells
A efficiency as one of the cells firing B is increased
when A and B fire AP at the same time
the connection / synapse between them becomes stronger
synaptic plasticity
The strength of synaptic communication between 2 neurons is not fixed
change in the strength of synaptic communications
how was long term potentiation first studied
recordings of fEPSP in performant pathway of rabbits
insert stimulating electrode into pathway
eject dendrite gyrus of hippocampus into dendritic field
record synaptic responses
experiments - change amplitude vs control
experiment to test hebbs law
evoke activity in A using stimulating electrode
see response in B
depolarisation of membrane potential to generate postsynaptic potential
general properties of LTP
input specificity
associativity
cooperatively
persistence
what is input specificity
LTP is induced selectively at a synapse or group of synapses that are formed between pre and post synaptic neuron
simultaneous activation of A and B - synapse between A and B is activated then this synapse will undergo LTP
what is associativity
a weak stimulus in one pathway is not sufficient to elicit LTP
when paired with activity in another strong pathway = LTP in both pathways
example of associativity (LTP)
A = weak
C = strong
if activity is just in A = B is not potentiated
is activity in A and C simultaneously = activity is elicited in B = both of the synaptic pathways undergo LTP
cooperatively if LTP
a weak stimulus in one pathway is not sufficient to elect LTP
when paired with another (does not have to be strong) pathway = LTP in both pathways
different between associativity and cooperatively
similar to associativity but does not require the second pathway to have a strong stimulus = just several input pathway activated at the same time
persistence LTP
increase in synaptic strength will last across time
after LTP occurred the AP is A will be more likely to drive an AP in its postsynaptic partner B
what is LTP induced by
high frequency conditioning stimulation
what receptors are required for LTP at a synapse
NMDA
why are NMDA receptors coincidence detectors
they detect presynaptic activity / glutamate
detect postsynaptic activity / depolarisation too
when are NMDA receptors activated
depolarised potentials
how are NMDA receptors blocked at polarised potentials
NMDA receptors
hyperpolarised/polarised potentials
magnesium ion blocks channel pore
prevents other ions moving across
when glutamate binds to NMDA receptors
glutamate binds
magnesium ion block is removed
so now with glutamate ions can pads through channel pore into post synaptic cell
what is needed to get LTP in NMDA receptors
Glutamate and depolarisation at the same time
= LTP
why does NMDA receptors activation lead to LTP
allow calcium to enter
influence In facilitating LTPs
why can’t AMPA activation lead to LTP
AMPA = allows movement of sodium ions
not calcium ions
experiment of calcium on LTP
CA3 to CA1 synapses in hippocampus brain slices
EPSP
number of cells filled with calcium chelator (nitr5)
high frequency stimulus
cells filled with nitr5 = take up calcium - can’t undergo LYP
shows calcium is essential for LTP
calcium effect on LTP
binding of calcium to calmodulin to CaMKII enzymes
causes a conformational change
active sites of the enzyme are released
able to go and act on downstream effectors
what intracellular signalling cascades does calcium activate
ca2+/calmodulin kinase
protein kinase C
calpaan
G protein
adenylyl cycles
what are the mechanisms by which LTP is expressed
- change in release properties (presynaptic)
- change in AMPAR properties (postsynaptic)
*chnage in AMPAR numbers (postsynaptic)
*synaptic growth (pre or post)
what requires LTP to be induced in CA3 to CA1 synapses in hippocampus
Presynaptic glutamate release
Depolarisation of postsynaptic cell
Removal of the mg2+ block from NMDA receptors
Long term depression
prolonged low frequency stimulation
what do some forms of LTD depend on
NMDA receptor activation and Calum postsynaptic entry
what can block LTD
intracellular calcium chelation using BAPTA
LTD can be induced by
Activation of metabotropic glutamate receptors
activation of muscarinic ACh receptors
3 processes involved in memory
encoding
consolidation
recall
how do neuronal networks remember things
plasticity = enable strengthening of connections = information is now embedded in connectivity between the neurons involved in coding the stimulus
when the input is reactivated by a stimulus the activity is Abel to drive the reactivation of neurons with the network =beacuse of increase strength of connectivity
too much LTP leads to
epilepsy
too much LTP leads to
epilepsy
LTP or LDP
HSF = NMDA receptor activation = LTP
LFS = NMDA receptor activation, MGLuR activation, mACh activation = LTD
different patterns of synaptic and NMDA receptor activation leads to different outcomes = LTP or LPD
