Lecture 19 (Memory & Hippocampus)

Long-Term Potentiation

“Fire together, Wire Together”

Altering a Synapse: LTP

• MG+2 ion blocks the opening of the NMDA receptor

• The binding of glutamate to AMPA receptor leads to depolarization (NA+ rush in)

• Continuous and strong depolarization boots MG+2 out NMDA

• Then calcium enters the cell + activate second messenger cascades to induce long lasting changes

  • Transportation of the intracellular AMPA receptors to membrane

  • Change in gene expression resulting in production of more AMPA receptors

Thought Experiment

Daniel Day-Lewis

• First watch a movie with this actor, strengthening the connections between neurons, and you watch another film with Lewis, reminding you of the first film.

• Pattern Completion

Pattern Completion

• Reinstatement of a memory from a partial cue

Hippocampus supports memory formation with LTP

• During the experience, activity patterns strengthen specific connections in the local circuit

• Activating a subset of the original representation results in “reinstatement” of OG exp (Pattern Completion)

Hippocampus Role in Memory of Rodents

• Mice trained to locate the position of a baited arm with food

• With data for 1 day vs 30 days with control and lesioned hippocampus group

• Found that the inactivation of the hippocampus disrupted Day 1 but remote memory retrieval was not affected

• Hippocampus is bidirectionally connected to the context

Two Stage Model

Ratatouille critic eatting the dish as a child

• The olfactory cortex encodes the odor and sends info to the entorhinal cortex, then to the hippocampus which it stores it post-exp

• LTP process temporarily stores info + exp strengthens synapses in the hippocampus, info of the ratatouille cleared out of cortex

• In sleep the hippocampus repeatedly sends the info back to the cortex (memory consolidation)

• Over a period of time, end result creates representations ingrained in the cortex

Memory Consolidation

• In sleep, the info of the exp in hippocampus repeatedly is being sent back and forth to the cortex

• Leaving the lasting memory of exp in the cortex

Reason for H.M. retaining his childhood memories

• Suggest hippocampus has a critical BUT time-limited role in memory

Systems-Level Memory Formation

• During experience (“online”) - Information is temporarily stored in the hippocampus through LTP (Memory Coding)

• After Experience (“offline”) the info gradually transferred from the hippocampus to the cortex (memory consolidation) while in sleep

Electrophysiological Recordings Role in Two-Stage Model

• Explain what neurons do in rodent hippocampus responses during exp

• Experiment: Rat ran across track and recorded firing of neurons

• Findings: Certain cells fire when in a specific location/space (place cells)

Place Cells

Certain cells that fire when animal is in a specific location or space

Hippocampal Replay

Time-compressed re-occurrence of the same sequence of place cell firing as during a recent behavior

• Reflect recent experience

• Generated in the hippocampus

• Prominent sleep

• Supports learning

Thought Experiment

• Says cortex is the “slow learner” and is less plastic vs hippocampus “fast learner”