Lecture 18: Molecular mechanisms of learning and memory

Memory Acquisition

• creation of new memories based on sensory experience (classical conditioning)

Memory Consolidation

• Process by which some memories are selected for long term memory storage (really emotional/important events)

Memories are stored in a distributed network

• Memories are stored in distributed networks of neurons

• Before learning, neurons have no stimulus selectivity

• After learning, neural patterns of stimulus selectivity emerge—it is the pattern of activity across the network—not indiivdual neurons that code different stimulus

Graceful Degradation

• memories get blended together rather than catastrophically lost all at once

• Tends to happen with age-related memory loss or brain disease

Learning and memory in aplysia

• When siphon stimulation is paired with a tail shock, the gill withdraws more quickly

  • sensitization

• At baseline, siphon stimulation causes an EPSP in the gill motor neuron

• Tail shock causes serotonin release on the siphon sensory axon terminal, activating G-protein signaling downstream of the serotonin receptor

• After sensitization, siphon stimulation causes a bigger EPSP in the gill motor neuron, resulting in more gill motor neuron firing

Synaptic plasticity

• Ability of synapses to strengthen or weaken

• Long term potentiation: neurons that fire together wire together

• Long term depression: neurons that fire out of sync lose their link

Long-Term Potentiation

• Once AMPA receptor is depolarized by glutamate, it will eventually cause the Mg2+ block in the NMDA receptor to be removed

• This allows Ca2+ to flow into the NMDA receptor

  • glutamate release presynaptically and strong depolarization postsynaptically

• Leads to AMPAfication

How does AMPAfication occur in LTP?

• AMPAfication leads to a larger postsynaptic response to the same input in the future

• Ca2+ entry into the cell when NMDA receptors open with strong depolarization activates protein kinases:

  • 1.) phosphorylate AMPA receptors (making them more sensitive to glutamate)

  • 2.) stimulate the insertion of new AMPA receptors

LTP can also lead to the growth/formation of new synapses

• In response to LTP, neurons can make synapses bigger or even grow new ones to provide more space for more AMPA receptors and therefore neurotransmission

Long Term Depression

• If synaptic inputs are coming in, but they don’t sync up with other inputs, then the postsynaptic membrane is only weakly or moderately polarized

  • Triggers AMPA receptor internalization and LTP

    • low Ca2+ influx activates protein phosphates which leads to the internalization (removal) of AMPA receptors

Memory Consolidation

• For consolidation into long-term memory new protein synthesis is required

• Newly synthesized proteins likely contribute to many things, but likely the formation of new synapses

• Long term memory can be accompanied by as much as a doubling of new synapses