Project Overview

We remember our experiences in the correct order and we can assess the elapsed time between them. Patients with damage in the hippocampus brain region cannot remember the order and time of experienced events, even though they can remember those events. Therefore, the hippocampus links together memories close in time, but how this occurs in the cellular level is unresolved. A possible mechanism is the sequential activation of groups of hippocampus nerve cells when an experience needs to be remembered. These sequences retain information on the memory of the cue and the time since its presentation. Their disruption may lead to disorganized memories. Indeed, patients with schizophrenia exhibit memory deficits and impaired time perception and may have disordered circuits in their hippocampus. It is therefore crucial to understand how these sequences are generated and how they get disrupted. Their generation requires close coordination between excitatory cells and a variety of inhibitory cells. But how inhibitory cells participate in sequences is unknown.

We will discover the activation patterns of two major types of inhibitory cells in the hippocampus. We will record these cells in mice while they perform a memory task, using a revolutionary microscopy technique that provides unprecedented time-resolution, cell specificity and the ability to track cells across days while animals learn the task. We will then apply this microscopy technique to determine how inhibitory cells misfire in schizophrenia. We will use a mouse model of a human genetic mutation associated with schizophrenia. This mouse combines poor memory and disordered circuits in the hippocampus.

This research will reveal the role of inhibitory cells in sculpting memory-linking activity in the brain and how this role goes awry in schizophrenia. It will yield powerful insights on how to restore dysfunctional activity in the brain, setting a path to future clinical applications.

Principal Investigator

Jiannis Taxidis , The Hospital for Sick Children

Partners and Donors

Azrieli Foundation