Project Summary: The hippocampus holds a major role in the encoding of new memories and their maintenance over time. Despite the fact that the hippocampal synapses are well characterized, the exact mechanisms governing memory formation and maintenance of remote memory is poorly understood.The hippocampus has been shown to encode spatial and contextual memories and short-term memories seem more strongly dependent on its activity than long-term episodes that are being supposedly maintained in cortical areas. But recent findings shed light on the participation of the hippocampus in the preservation of long-term memory precision. This crucial function seems to be regulated by the feedforward inhibition from the Dentate Gyrus (DG) onto the CA3 region of hippocampus. Actin Binding LIM 3 protein (Ablim3) has been identified as a key regulatory factor of the contact between DG cells mossy fiber terminals onto CA3 inhibitory interneurons. Ablim3 levels are reduced during learning in mice and are associated with a greater connectivity between DG cells and CA3 interneurons. The same outcome was observed when virally downregulating Ablim3 levels. Increased connectivity between the DG and CA3 interneurons strengthen feedforward inhibition onto CA3 principal neurons and improves precision of long-term memory; in contextual fear conditioning paradigm mice with downregulated Ablim3 performed better in remote memory recall than control animals.

Our interest is now focused on the neuron population dynamics in memory-associated hippocampal and cortical regions and how these dynamics are altered by the downregulation of Ablim3. To investigate those questions we use in-vivo 1-photon Calcium imaging, a powerful tool that allows live imaging a neuron population at single-cell level with fairly good temporal resolution. This will give us an understanding of the evolution of neuron dynamics of a memory from its encoding to its long-term recall and observe how well sustained are the population’s properties along this time line. We aim at discovering how manipulation with the feedforward inhibition from DG onto CA3 influences the neural code of memory.

My project focuses on the imaging of the anterior cingulate cortex (ACC), a strong candidate for the storage of long-term memories. It is hypothesized that ACC receives downstream influence of the feedforward inhibition from DG onto CA3 via CA1. My goal is to investigate this dependence and assess the neuron dynamics in ACC in a contextual fear conditioning paradigm, probing neuronal activity at different time points using calcium imaging. I hope to relate my results with those found in hippocampal regions to better characterize the link between hippocampal feedforward inhibition and long-term memory maintenance.