Maturation of Circuits Underlying Learning and Memory

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Our perceptual, cognitive and emotional abilities emerge at specific times during development and are critically shaped by experiences that occur during early life. Early development is also a period during which key brain areas involved in emotional processing, such as the hippocampus and prefrontal cortex, are maturing. This maturation coincides with the emergence of behaviours dependent on hippocampus-prefrontal cortex networks, such as the ability to generate long lasting memories, or memory persistence. Despite convergent evidence of volumetric, structural, and synaptic changes taking place in prefrontal cortex and hippocampus at the same time as memory persistence emerges, no study to date has looked at how the functional maturation of the hippocampus-prefrontal cortex circuit contributes to the ontogeny of memory persistence. To address this gap in knowledge we will use optogenetic tools to study how synaptic connectivity between hippocampus and prefrontal cortex changes across development. These are pressing research questions since presently there is no information on how the maturation of brain circuits underlying learning and memory might affect cognitive function in adulthood. ******To answer these questions, we will: (1) examine the maturation of basal synaptic transmission and anatomical connectivity within this microcircuit, (2) uncover the relationship between hippocampus-prefrontal cortex synaptic plasticity and the ontogeny of memory persistence, and (3) manipulate these plasticity changes in vivo to test whether this interferes with the onset of this behaviour. To fully describe hippocampus-prefrontal cortex functional maturation across development, we will use a combination of histological, electrophysiological and behavioural techniques. Despite the emergent use of optogenetics for the functional dissection of brain microcircuits, the use of this technique within the context of development is both powerful and as yet unexplored.******This research will advance knowledge in three ways. First, it will establish a novel framework for the study of complex behaviour from the standpoint of the functional maturation of brain circuits, providing critical insight applicable to any number of developmentally regulated behaviours. Second, it will help define the circuit requirements necessary to sustain memory persistence, a process at the core of cognitive function. Third, identifying periods of heightened plasticity within the maturation of circuits underlying emotional learning has significant implications for interventions. Mapping the factors curtailing plasticity in learning and memory circuits will guide the design of circuit-specific interventions to enhance learning, improving the socioeconomic status of thousands of young Canadians in this and future generations.