It has become recently possible to identify engram neurons holding memory traces in the brain, by tagging them with actuators to specifically ablate or activate them in relation to a memory task. However, a whole neuron is unlikely to be the unitary substrate of memory and there is a gap between the classic field of synaptic plasticity studies and the emerging field of cell engrams. To fill this gap, a leap from the cellular to the synaptic level is required. We define a synaptic engram as a population of tagged synapses that are necessary and sufficient for the establishment of a given memory. However, ways to experimentally demonstrate synaptic engrams by selectively controlling the activity of potentiated spines were lacking until recently. Prof. Antonino Cattaneo has recently developed a new method to achieve the local expression of actuators at potentiated synapses, enabling their selective tagging following the encoding of a memory. The overarching aim of the project is to exploit this strategy to to enquire to what extent microglia orchestrate and contributes to the induction/formation and consolidation of synaptic memory engrams. This innovative project will allow a quantum leap in our understanding of memory processes.
The project addresses a long-standing question regarding the mechanisms of memory. Decades of synaptic plasticity studies have allowed formulating a paradigm whereby long lasting changes in the synaptic connectivity between neurons are crucial for the establishment and maintenance of memories. On the other hand, engram neurons involved in specific memories have been recently identified. There is a clear spatial scale gap between the field of synaptic plasticity studies and the emerging field of cell engrams and a comprehensive integration of the two fields in a unitary, formulation is lacking. The project aims at filling this gap and will provide important advances on the microglia-synapse crosstalk in memory formation, maturation and storage. The project incorporates new technological approaches towards this goal, which would also provide precious information on their own. Finally, the project will investigate synaptic engrams-microglia interaction to regulate and mediate synaptic plasticity.