+Empirically Testing "A Proposed Function for Hippocampal Theta Rhythm"

TEAM MEMBERS:

• Katie Geimer (Project Lead)

• Audrey Ott

PROJECT DESCRIPTION:

Background

In 2002, Michael Hasselmo et. al. published a modeling paper which hypothesized that phase locking of the theta rhythm relates to the encoding and retrieval of memories. By this theory, memories are made (encoded) at the trough of theta and that memories are remembered (retrieved) at the peak. An implication of this phase locking is that the destruction of the theta rhythm disrupts encoding and retrieving, making a person, or in our case a rat, unable to make new memories. A few of the above concepts are helpfully explained here:

• General anatomy of the human hippocampus

• Hippocampal theta rhythm and how brainwaves are formed

• Phase precession and encoding and retrieval

The goal of this research is to empirically test Hasselmo's hypothesis of the importance of phase locking in the encoding and retrieval of memories. This modeled but empirically untested hypothesis has been central to the scientific community's understanding of the hippocampus and has been cited 553 times since its publishing in 2002. However, there are currently no publications of experiments which empirically tested the hypothesis. The implications of testing this theory include a more robust understanding of the hippocampus and its functions.

Methods

This is an electrophysiology project, meaning we build electrodes, implant them into the brain, record data during a behavioral task, then complete subsequent data analysis. The two types of data we collect that are important to understand before reading further are:

• Local field potential (LFP)

• 'Spiking data' otherwise known as action potentials

The timeline of the methods follows:

1. Building recording apparatus & surgical implantation

1. Post-surgery, electrodes were stepped down through a process called turning to hippocampal CA1

3. Animal training and data collection

• 1. Exploration:

     • Implanted rats are placed into the maze at the bottom of the middle arm and are allowed to explore for one 15-minute session. Fragments of Froot Loops are placed around the maze to encourage exploration and comfort.

  2. Trial Setup:

     • There are two food reward bowls - one down the arm to the right from center and one to the left. At any point only one will have a reward.

  3. Phase 1: Training

     • The rat is placed into the the maze at the bottom of the middle arm. He is free to choose which direction to run, but only one food dish contains Froot Loops (for example, Right/Blue). The reward is continuously found in the Right reward site until the rat is fully trained to go to the right for food reward.

  4. Phase 2: Reversal

     • The rat is run as normal for the first 15-20 laps of the trial. Then the reward is switched to the other (Left) reward site. Now the reward appears consistently to the left.

  5. Phase 3: Second Reversal

     • Following the procedure as above, a second reversal is optional.

4. Spike Sorting

1. Different analyses are completed for each phase of the project, though generally concerned with looking at temporal and spatial coding of cells