Lecture 11 and 12 - LTP and LTD mechanisms Flashcards
with is a Hebbian synpase
- coordinated activity of a presynaptic terminal and a postsynaptic neuron to strengthen the synaptic connections between them
recording the LTP phenomenon
use CA1 neuron and record from it and have presynaptic inputs of the neuron resulting in a response
- expect the EPSP with stable amplitude of change
- record many times and average should be the same
what happens to the amplitude on average for LTP phenomenon?
amplitude on average becomes bigger to lead to a higher firing rate and other processes
what does higher frequency result in for LTP phenomenon
- high frequency leads to higher and longer activity in postsynaptic neuron
- EPSP becomes bigger
what happens when the neuron receives multiple inputs?
- get an increases in amplitude in input 1
- stimulate input 2 will remain the same
- there are places in the neuron where LTP is not shared
what happens when two pathways converge on the same target?
- they can be strengthened if they fire together
- one pathway may be quite weak
how to get an LTP phenomenon in both neurons
stimulate both neurons at the same time and both depolarise
what is the synpase bwteen CA3 and CA1
glutaminergic
what are the three classes of glutamate receptors?
NMDA, non-NMDA and mGlut
- NMDA and non-NMDA are ionotropic
- mGlut are metabotropic
AMPA (non-NMDA) permeability
more permeable for sodium and potassium and is the main receptor for transmission of information
NMDA permeability
permeable to calcium so does not depolarise the cell much but increases calcium concentration
how does LTP occur? (CamK2)
NMDA opens and leads to increase in calcium concentration and activates kinases like CamK2 which is activated by calcium. Kinase phosphorylates different proteins which leads to increase in amplitude of EPSP
magnesium dependent magnesium block in NMDA receptors
just glutamate alone is not enough, needs to depolarise the cell as well and leads to activation of the receptor as it removes magnesium
weak vs strong activation (AMPA and NMDA)
if activation is weak only AMPA will open. If there is strong activation, the magnesium block is removed and the NMDA receptor is activated
early vs late LTP
- early involves activated NMDA receptors with Camk2 self phosphorylation leading to AMPAification
- late involves gene expression with CREB2 binding to CRE
cerebellum LTD circuitry inputs
positively charges mossy and climbing fibres
cerebellum LTD circuitry outputs
negatively charges Purkinje fibres
cerebellum LTD circuitry
mossy fibres send signal to granule cells (parallel fibres) which send signal to Purkinje fibres (by climbing fibres)
what evokes LTD?
- paired Purkinje fibres and climbing fibres to a signle Purkinje cell
which channels does cerebellar LTD mechanisms involve?
metabotropic Glu-R, AMPA-R, and voltage-activated Ca2+ channels
cerebellar LTD mechanism
- protein kinase C phosphorylates AMPA GluR2 subunit
- reduces currents by endocytosis
- CF transmitter is glutamate
- AMPA-R internalisation triggered by phosphorylation
what inhibits LTD?
Endocytosis inhibitors
where does LTD occur in hippocampus?
CA3-CA1 synapse with LFS
what dictates the probability of inducing LTP or LTD?
the degree of NMDA receptor activation
what reduces AMPA-R efficacy?
small increases in calcium from NMDA-R triggering more phosphotase action
what increases AMPA-R efficacy?
large increases in calcium activating more protein kinases
