Learning and Memory 1 Flashcards
What is learning?
Learning is a response of the brain to environmental events - brain plasticity allows for learning. Donald Hebb (1949) - “cells that fire together wire together”.
Example of learning in the hippocampus
Hippocampal neuron with inputs from cell A (sensory input for sight of rose), cell B (sensory input for smell of rose), and cell C (sensory input for smell of onion). If that association is made frequently, this synapse will be strengthened, and sight can stimulate hippocampal memory and generate memory of the smell – this is due to association of neuron. Strengthening is synapse specific – strength of one synapse won’t change – association of one smell will be separate to the smell of another.
What is long term potentiation? (LTP)
Mechanism underlying synaptic strengthening. After high frequency stimulation, the response changes - the response is much greater than it was prior to stimulation. This increased response lasts a long time. This change is stimulus = LTP.
What is temporal LTP?
Summation of inputs reaches a stimulus threshold that leads to the induction of LTP. e.g. Repetitive stimulation (HFS).
What is associative LTP?
Simultaneous stimulation of a strong and weak pathway will induce LTP at both pathways. (Spatial summation)
Coincidence detection
“Cells that fire together wire together”.
What is specific LTP?
LTP at one synapse is not propagated to adjacent synapses (input specific).
What’s happening at the synapse when glutamate is released onto an inactive vs. active cell?
Glutamate is released onto an inactive cell (membrane at resting potential). AMPA receptor is activated to create EPSP, NMDA receptor blocked by Mg2+ ion. Depolarisation from AMPA activation not sufficient to expel Mg2+.
Glutamate is released onto an active cell (membrane depolarised_. AMPA receptor is activated. Mg2+ block on NMDA receptor is relieved. Calcium triggers a pathway of events which triggers change in the postsynaptic cell - next time this is activated, it’s going to have a different effect. By calcium entry, immediately in post-synaptic membrane will have more AMPA receptors, and these AMPA receptors act more efficiently. Can therefore increase the size of EPSPs. This change is the long-term potentiation.
What is a molecular switch?
Calcium entry through NMDA receptor leads to activation of CaMKII. This becomes phosphorylated (means is constitutively active, and does not need calcium). Molecular switch maintains increased excitability of neuron for minutes - hours. Able to keep itself in a potentiated state.
What are presynaptic events in LTP?
Nitric oxide synthase – at activated synapse where have calcium into neuron, will make nitric oxide into neuron which will diffuse through membrane (gas). This nitric oxide will diffuse into presynaptic terminal. Here have pathway which is activated by nitric oxide, which produces guanylvl cyclase. This increases the amount of glutamate have in presynaptic terminal ready for release. Not only are boosting activity of presynaptic terminal, but also causing it to have more glutamate ready for release. Response of glutamate will therefore be amplified across the synapse.
What is late phase of LTP?
Requires new proteins to be made that can change the properties of the synapse. Protein synthesis inhibitors prevent the consolidation of longterm memories and LTP. Stages of memory formation are acquisition, consolidation, and recall.
What is early vs. late phase LTP?
Early phase LTP lasts a minute - an hour, and can be explained by the actions of calcium through the NMDA receptor and subsequent enhancement of AMPA receptor efficiency.
Late phase LTP lasts hours, days, or months - requires new synthesis and can involve morphological changes & the establishment of new synapses.
What is recruitment of new synapses in LTP?
Neurons will have multiple synapses from one cell to another. In normal conditions, only middle synapse would be activated. This is why the others is called a silent synapse – stimulation blocked by magnesium. Under high frequency stimulation, silent synapse would become active (glutamate would become active) as activity spreads across the membrane. Now have three synapses with AMPA receptors, and therefore have tripled the response.
With protein synthesis changes, get synapse changes (get increase number of synapses).
How is there an increase in the number of synapses in LTP?
During tetanic stimulation, see spines starting to pert rude from the dendrite (new synapses). This keeps process of LTP to last for hours/days.
What is Long Term Depression?
Low frequency stimulation results in a decrease in EPSP amplitude. It is still a NMDA dependent process: AMPA receptors are dephosphorylated and removed from the membrane. Low level rises in calcium active phosphatase rather than kinase.
What is the Morris Water Mate experiment?
Pool of water that has a platform that is hidden, give rats external clues and see how long it takes to learn where that platform is. Destroyed hippocampus from rats, then tested control rats with rats with hippocampus missing. Rat with no hippocampus cannot learn where the platform is. For this type of learing and memory (spatial memory), hippocampus is essential.
