Causal assessment of bilateral CA3-CA1 communication in hippocampal content representation

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The hippocampus processes information about the spatial environment an animal is in ('context') and the items, odours and sounds ('content') present within this environment. This project aims to assess the neuronal circuit mechanisms underlying context-content binding in the hippocampus.
We have recently demonstrated a central contribution for the left CA3 neurons in a hippocampus-dependent associative learning task in mice. In the first phase of our project we will therefore record extracellular field potentials and multiple single-unit activities bilaterally from the mouse CA3 and CA1 subfields during learning. Mice will learn to associate either a location or an item with reward in two separate contexts. This will reveal whether learning modulation of place cell firing (e.g., changes in firing rate, place cell numbers or population synchrony) is distinct across the CA3 and CA1 subfields, whether it occurs preferentially in the left compared to right CA3, and whether any cross-hippocampi asymmetry observed is task dependent.

In phase 2 of the project we will address the causal relationship between the CA3 and CA1 during learning using optogenetic projection silencing informed by findings from phase 1. Such an analysis will allow us to understand the routing of information across hippocampal subfields and hence the types of computations task relevant 'content' information has to go through before reaching the CA1 subfield, the major output of the hippocampus.
Phase 3 will look at the reactivation of hippocampal cell assemblies during sleep-associated sharp wave-ripple (SWR) network events following learning. We will furthermore assess the necessity of SWRs arising in left and/or right CA3 in memory consolidation using an optogenetic feedback loop silencing system.

The proposed project deals with the network-level mechanisms underlying learning and memory processes during complex
behaviour. It is thus well positioned to have a broad impact, particularly on the educational front. This will involve both
communicating the broad aspects of memory research in general and more project specific information. On the broad front,
we will communicate some of the basics of neuronal network function during learning to schools and during science
festivals and departmental open days. On the project specific front, we will emphasize the impact of learning and sleep on
neural activity associated with the persistence of memory and education to teachers and students. In particular, we will
communicate our findings regarding the causal contribution of certain activity states to memory stability and emphasize
how this may impact on sleep related interventions in an educational setting. We also envisage that our analysis of cell
assembly dynamics during learning will reveal novel insights into learning computations that can be used in the machine
learning field to optimize learning algorithms. We intend to work closely with researchers in the machine learning field in
both Oxford and Cambridge University. In all of these interactions, we will ensure communication is bidirectional, making
use of feedback gained from the educational and machine learning fields to inform our own research activities.