Lecture 18 Flashcards
Learning and memory
Learning - the process by which experiences change our nervous system and thus our behavior
Changes called memories
Accessing memories is called retrieval
Cellular basis is neuronal plasticity (just means nervous system can change and adapt)
For a while they looked for an area for memory, could not find it. Then thought maybe its just ongoing activity but after sleep or a seizure, memories exist so this cannot be true (ight be for STM). Eventually realized it could be globally distributed and involved synaptic modification
Intrinsic and extrinsic excitability
Intrinsic - the number of action potentials a neuron exhibits in response to the influx of positive current
Synaptic strength, the amount of positive (or negative) current that enters the postsynaptic neuron when the presynaptic cell has an AP
A change in this synaptic strength is called synaptic plasticity.
Measurement of intrinsic excitability
Insert wire to measure
Measure baseline
Put charge in
Se firing rate
If a neuron starts to express fewer leak channels, it will become more excitable (more APs for the same input)
Synaptic plasticity
Changes in strength of synapse between two neurons
Enduring changes called Long term potentiation (TTP) and long term depression (LTD)
EPSP excitatory post synaptic potentials are membrane depolarizations evoked by some number of synaptic inputs
To measure these, put wires in pre and post cells. Send current through pre to give post an EPSP but sub threshold cos you need to be able to measure the magnitude. Can see it gaining with time.
Can involve pre and post changes
Pre might include voltage gated calcium channel; expression
Post might include NT receptor expression
Non associative learning: habituation and sensitisation
Use Aplysia (sea slug)
If you tough the siphon, gill withdrawal
Repeated light touching reduces the withdrawal until it ignores it - habituation (drop)
If you shock it repeatedly, response goes up - sensitization
Sea slug habituation
Excitability of the sensory neuron changed
Less NT released
Brain slice method
Treat brain
Keep cold cos then low oxygen requirement
slice thin
put in artificial CSF
add oxygen and glucose (can diffuse cos thin)
Use two neuropippets, add one to pre and one to post cells
Cut cell membranes join up again
Gain access via neuropippet to fluid (so whatever is in pippet can diffuse in) and to electrical access
Can stimulate with one and record with another
Log term potentiation
Increase in strength of connection of two neurons
Repeated high strength tetanic simulation of a neuron often induces LTP (100Hz for 1 second, 4x)
LTP is begun on post-synaptic side. This then sends NO to drive presynaptic modifications via retrograde signaling
Short term potentiation
Decrease in synaptic strength
Persistent low f stimulations often causes LTD. 1Hz for 10 mins
Initiated on postsynaptic side but endocannabinoid signaling can cause presynaptic modification
Synaptic plasticity: LTP LTD
High f for 1 second = LTP
Low f over a long time = LTD
LTP and LTD are influenced by the amount the synapse was active and whether the post synaptic cell fired at those times
High f stimulation causes downstream neurons to spike due to summation of EPSPs. Low f stimulation does not.
For LTP to occur, the release of NT must coincide with a substantial depolarization of the postsynaptic cell
The NMDA receptor
Is an ionotropic glutamate receptor that has a large ion pore. When NMDA receptors bind glucose, they open.
If the cells membrane potential is below threshold (-40mV) Mg2+ ions try to rush in but get stuck
If it is depolarized (more than -40mV0 this wont happen because the cell is not strongly negative enough to attract the Mg2+ ions and so they wont clog the pore
So current flow through NMDA receptors is gated both by glutamate and membrane voltage. Na+ and Ca+ ions will enter through NMDA receptors ONLY when those receptors are bound to glutamate and not clogged by Mg2+
The NMDA receptor plays a big role in learning and memory, they are located at almost every glutaminergic synapse in the brain
AMPA receptor/NMDA receptor CaMK11
AMPA receptor = the glutamate receptor that mediates most fast excitatory synaptic currents in the brain
Lets in Na+ which cause EPSPs
NMDA receptor = Ionotropic glutamate receptor that only passes current when glutamate binds and the cell is slightly depolarized. If hyperpolarized, gets blocked by Mg2+
CDK11 = Type 2 calcium-calmodulin kinase. An enzyme that is activated by calcium influx through NMDA receptors. Does a cascade which establishes long term potentiation by increasing the amount of post synaptic AMPA receptors in the synapse
Dendritic spine growth as LTP
These develop as more AMPA receptors are made.
LTP on pre synaptic membranes
Happens but post synaptic neurons initiate things.
They release NO as a retrograde messenger to promote LTP
CAM-K11
(1) the mRNA for PKM-zeta is constantly transcribed in the nucleus and transported to dendritic spines but its translation is constantly blocked by Pin1
(2) When LTP conditions are met, Ca2+ ions enter the cell. They activate CAM-KN11. This suppresses the action of Pin1. Pkm-zeta mRNA is then translated into PKM-zeta protein which activates the enzyme NSF.
(3) NSF initiates the movement of AMPA receptors into the dendritic spine
(4) PKM-zeta protein also inhibits Pin1 and so ensures that PKM-zeta protein keep being made
