PRE2023-Sources and machinery of synapse heterogeneity-PID2022143237OB-I00

Excitatory synapses represent the primary means for communication within neural circuits and provide control points for information processing and storage. A diverse set of synapses is utilized across neuronal populations and circuits. Some of the heterogeneity involves differences in synapse ability to undergo plastic changes. Here a correct balance between mechanisms that support transient vs long-lasting synaptic changes is thought to be key for optimizing cognitive-based behavioral strategies by determining the types of information that are flexibly or persistently encoded as memories. Yet the mechanisms engaged during dynamic information processing are poorly understood. The project will address the contribution of a special type of brain receptors (non-conventional GluN3A-NMDA receptor). Highly expressed in young brains, GluN3A-NMDARs oppose lasting forms of synapse plasticity to confer precision to mature neural circuits. Adult expression is retained in defined brain territories, cell populations and subsets of synapses. We hypothesize that adult GluN3A-NMDARs provide niches for juvenile palsticity and are conduits for short-term, flexible information. The specific project will use: i) conventional/Crispr/viral genetics, or proximity-labelling proteomics to unravel the roles of non-conventional NMDA receptors in specific neuronal populations and identify the synaptic pathways and mechanisms, ii) start exploring sources of heterogeneity at the presynaptic level.