Title: Hippocampal circuit dynamics and memory processes
Funder: Medical Research Council

Abstract: The hippocampus (HPC) is a neural circuit that provides the brain with a representation of space used to guide our daily behaviour. Indeed, hippocampal pyramidal cells – known as place cells – discharge action potentials in relation to the subject’s location so that, at the population level, their joint activities map the entire environment. Numerous studies now clearly support the view that firing patterns of place cell assemblies underlie the formation and expression of spatial memory traces in the HPC. However a comprehensive explanation of memory processes requires an integrated investigation of brain circuits, with emphasis on revealing the contribution of inhibitory interneurons and well-defined network oscillatory patterns. Moreover the persistence of hippocampus-dependent memories is subject to extra-hippocampal neuromodulatory signals such as those coming from the dopaminergic neurons of the ventral tegmental area (VTA) involved in reward-information processing. Finally, once computed hippocampal mnemonic patterns propagate to several synaptically-connected circuits, including the nucleus accumbens (NAc) of the basal ganglia involved in action selection and goal-directed behaviours. Recent evidence indicates that the HPC-VTA-NAc system is a key tripartite circuit to establish place-reward associations used to guide behavioural actions according to the spatial context. The unmet research challenge of this programme is to determine how HPC-VTA-NAc neuronal dynamics operate during the encoding, storage and retrieval of spatial and reward information for the purpose of goal-directed behaviour. This programme contains 4 specific scientific objectives: 1: To describe hippocampal pyramidal cell-interneuron microcircuit dynamics during spatial learning 2: To identify the contribution of sleep-related hippocampal oscillations in memory consolidation 3: To test whether dopaminergic VTA neurons modulate mnemonic patterns of hippocampal assemblies 4: To investigate HPC-NAc network interactions during reward-seeking behaviour The main technique employed in this programme consists of performing large-scale electrophysiological recordings of neuronal activity from rodents during periods of waking behaviour and sleep. These recordings are combined with optogenetic techniques in order to investigate, with high temporal precision, the contribution of specific populations of neuron or specific network oscillatory patterns. These experiments are providing unique data on the behavioural significance of neurons in brain regions regulating memory processes and adaptive behaviours This work will establish the fundamental principles by which interrelated activity of neurons in the HPC-VTA-NAc system provides the spatial framework within which reward-related information are processed to guide behavioural actions. Such an understanding is a timely question not only for understanding normal brain function but also for explaining what goes wrong in neurological and psychiatric diseases and thus, how best to treat them.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: NEUROLOGICAL