Dynamics of cell assemblies underlying adaptive and mal-adaptive memories

Learning and memory processes rely on the fine coordination of nerve cell activity in several brain regions including the hippocampus and the nucleus accumbens. In this programme we aim to explain how and why nerve activity is organised, not only for understanding normal brain function but also for explaining what goes wrong during memory disorders, including those associating an environment with drugs of abuse. We seek to explain how nerve cells in these brain regions produce accurate patterns of electrical activity that are essential for our memory representations of environments in which salient life events have been experienced. In this work we use cutting edge technologies, ranging from the combined use of rodent behavioural paradigms and brain recordings to light-based manipulation of nerve cell activity. In so doing we place special emphasis on explaining when, why and how special patterns of electrical activity, such as waves or rhythms in different types of nerve cell assist brain operations during normal behaviours. By using light-based tools to experimentally interact with different cell types in these brain circuits we identify patterns of electrical activity that might support abnormal behaviours. In conclusion, this programme of research will allow us to provide novel insights into how nerve cells in the brain coordinate their activity to guide so much of our daily behaviour in both health and disease.

Memory is central to behaviour, enabling individuals to infer from past experience how to respond to their ever-changing environment. Nonetheless the recall of certain memory representations, such as those of environments where a drug of abuse was experienced, is undesirable as these can impair the individual’s ability to adapt to its environment and therefore put it at risk. In this programme our goal is to provide a mechanistic understanding of how temporally-structured neuronal activity in the brain underlies memory processes. To this end we seek to determine how pyramidal cell-interneuron dynamics underlie the temporal segregation of cell assemblies in the hippocampus for the coordination of the read-in/encoding of new information with the read-out/retrieval of old stored information. We further investigate how downstream network interactions with the nucleus accumbens mediate the guidance of purposeful behaviour by spatio-contextual memories. In this work, we use a number of complementary techniques to monitor and stimulate neuronal activity in the mouse brain during well-defined behaviour. In so doing, our programme will probe temporally patterned manipulations aimed at rebalancing brain dynamics by the selective enhancing, reprogramming or weakening of the cell assemblies providing brain representations of drug/fear-paired environments. This work is intended to provide principles of intervention of brain areas where network dynamics underlie pathophysiology of memories.