+Hippocampal Place Cell Ensembles Remain Intact Despite Disrupted Phase Precession

TEAM MEMBERS:

• Brianna Le (Former Project lead, graduated)

• Afnan Abdulahi (Project lead)

• Katie Geimer (Project lead)

• Audrey Heile

• Audrey Ott

PROJECT DESCRIPTION:

Background

This project takes a closer look at the interaction between the hippocampus and modulatory effects of acetylcholine which are both important for the encoding of new memories. A few concepts to understand before diving into more details of the project are:

• General anatomy of the hippocampus

• Hippocampal theta rhythm and how brainwaves are formed

• Phase precession

Hippocampal theta rhythm is often viewed as a clocking mechanism that coordinates the spiking activity of neurons across he hippocampus to form coherent cell ensembles. Phase precession by place cells in dorsal CA1 of the hippocampus, which is a process thought to arise from this clocking, was previously shown to be degraded under the influence of a cholinergic antagonist called scopolamine (Newman E et al, 2017) .This was seen while looking at individual place cells within the hippocampus. Are ensembles of these cells similarly affected? The next few sections will outline the the questions related to this overarching question that we are attempting to answer through various sequential projects .

1. Cholinergic antagonist reduced phase precession of spiking relative to theta- is this effect coherent across cells?

• 1. Data collection and analysis is complete, paper in progress

  2. Results indicate that coherence across cell ensembles- cell ensembles were intact after cholinergic blockade despite the loss of temporal coding

1. Since the effect is coherent- then what is causing the loss of phase precession?

   1. Looks at what is encoded in neural ensembles and is there a change in neural ensembles and is there a change in the content they are encoding?

   2. Experiment currently in progress

2. If content changes- what is the mechanism behind the change?

• 1. Considers relationship between effects and gamma

  2. Implications toward entorhinal cortex and hippocampal CA1 coupling

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. Before implantation, rats are trained to collect rewards around a circle track

  2. Implanted rats then collect rewards around the circle track while recording LFP and spiking data

     1. Baseline trial is collected without injection

     2. injection trial is taken (alternates between saline and scopolamine trials)

     3. Recovery trial is taken after injection has worn off

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

Five core papers to understand the project:

1. Newman EL, Venditto SJC, Climer JR, Petter EA, Gillet SN, Levy S (2017). Precise spike timing dynamics of hippocampal place cell activity sensitive to cholinergic disruption. Hippocampus.

2. Harris KD, Csicsvari J, Hirase H, Dragoi G, Buzsaki G (2003) Organization of cell assemblies in the hippocampus. Nature.

3. Dragoi G, Buzsaki G (2006). Temporal Encoding of Place Sequences by Hippocampal Cell Assemblies. Neuron.

4. Zhang, K., Ginzburg, I., McNaughton, B. L., & Sejnowski, T. J. (1998). Interpreting neuronal population activity by reconstruction: unified framework with application to hippocampal place cells. Journal of neurophysiology, 79(2), 1017-1044.

5. Gupta, A. S., Van Der Meer, M. A., Touretzky, D. S., & Redish, A. D. (2012). Segmentation of spatial experience by hippocampal theta sequences. Nature neuroscience, 15(7), 1032.