L19: Molecular Mechanisms of Learning and Memory Flashcards
Two stages of learning and memory
Acquisition of short term memory
Transition from sensory experience to a short term memory is acquisition
Memory acquisition occurs by a physical modification of the brain caused by incoming sensory information
Modifying synaptic transmission between neurons (temporary!)
Consolidation of long-term memory
Consolidation is the conversion of a short term memory to a long term memory
Distinction btwn short and long-term receptors
Short term memories tend to be in an active state. They are vulnerable to disruption and have rapid decay.
Long term memories are in an inactive state. They are less vulnerable to disruption and have slow decay.
progression of memory from short to long term is characterized by sensitivity to disruption. As we consolidate memory, they become more resistant to disruption due to the post acquisition processes involved in making memories long term.
How do neuronal synapses change over time?
First messenger—> neurotransmitter, bind to receptors and cause changes in the cell.
Second messenger—> inside the post synaptic cell. Lead to formation of proteins.
Different types of proteins lead to structural changes at the cellular level. Kinases and phosphates. Structural and functional proteins.
Focusing on excitatory cells within hippocampus
Glutamate is excitatory neurotransmitter.
There are 2 types of glutamate receptors. AMPA receptors and NMDA receptors. Both ligand gated, so if glutamate (ligand) binds to them, then they are able to operate. Clear distinction between them.
When glutamate binds to AMPA receptor, it allows sodium to enter the cell and depolarize it so there will be some sort of EPSP.
Pore of NMDA receptor is blocked by magnesium. Once the cell becomes depolarized because sodium enters through AMPA receptors, the magnesium will no longer be attracted to the NMDA receptor so it will leave and go into the synaptic space and calcium will be allowed into the cell. Calcium mediates all the secondary messengers. So NMDA receptor is both ligand and voltage gated.
Long term potentiation
Cells that fire together wire together
A long-lasting enhancement of the effectiveness of synaptic transmission (increase in synaptic strength)
This is mediated by changes in receptors.
Higher baseline and lasts for a longer period of time because of frequent activation of presynaptic cell.
Input specificity
Just because you have LTP at one cell does not mean that you will have LTP at a neighboring cell. Specific to the synapse where these processes are occurring
Cellular Changes
Even distribution of NMDA and AMPA receptors.
At baseline, AMPA-only activation.
When there is a tetanus, AMPA and NMDA activation. Calcium influx activates second messengers that insert more AMPA receptors into the postsynaptic membrane.
After: increased EPSPs relative to baseline given higher number of AMPA receptors.
Calcium induces changes is via enzymes called kinases.
2 different types of kinases
Protein kinase C (PKC)
Phosphorylates AMPA receptors to increase ion conductance so the AMPA can let in more sodium and allow the baseline to be higher up
CaMKII
Phosphorylates AMPA receptors to increase ion conductance
Induces vesicles with AMPA receptors to be inserted into the synapse
Inhibitory avoidance
Rat placed in box with a light side and a dark side. Rats prefer the dark side as they are nocturnal so they naturally go in there. But if they are shocked, then they will learn not to go to the light side and this learning will last a while.
Shows LTP and behavior because if you look at EPSP magnitude, it is much higher than baseline and lasts a while.
Long term depression
Opposite of LTP
A long-lasting decrease of effectiveness of synaptic transmission (decrease in synaptic strength)
Decoupling the cells
Input specificity persists. If you get LTD in one neuron, it does not mean that the neighboring neuron will also have LTD, it might just have LTP.
Baseline is lower and lasts.
Happens when post synaptic cell fires before pre synaptic cell and it decreases their relationship
Neurons that fire out of sync lost their link
Cellular changes facilitating LTD
Weak NMDA activation
Really little calcium coming in
PKC and CaMKII are not going to Phosphorylate and add more receptors to the membrane
Instead, receptors are pulled out of the membrane.
This is mediated by a new enzyme, phosphatase (protein phosphatase 1 or PP1 or calcineurin). It dephosphorylates the AMPA receptors and internalizes them, opposite effect of kinases
Comparing LTP to LTD
When comparing amount of NMDA activation during tetanic stimulation to long-term change in synaptic strength, weak NMDA activation causes LTD while stronger NMDA activation causes LTP.
Comparing time difference between post and presynaptic spiking. Negative difference causes LTD while positive difference causes LTP. Very little positive difference is highest LTP. Very little negative difference is most LTD.
