MAPPING GLUTAMATERGIC SYNAPTIC MATURATION DURING ADOLESCENCE

During adolescence glutamatergic synapses undergo rapid change. N-methyl-D-aspartate receptors (NMDARs) are found at excitatory glutamatergic synapses and are typically heterotetrametric, containing two GluN1 subunits and two GluN2 subunits which range from GluN2A-D. Subunits of glutamatergic receptors are highly influential to receptor properties and influence synaptic activity, particularly during adolescence when cognitive functions mature. However, the specific glutamatergic changes required to facilitated synaptic maturation in adolescence has not been well characterised. To understand which regions, undergo glutamatergic synapse maturation during adolescence, we performed whole brain high-throughput imaging of mouse lines expressing knock-in fluorescent reporters for postsynaptic scaffolding proteins: postsynaptic density 95 (PSD95)-eGFP and synapse-associated protein (SAP102)-mKO2 (Zhu et al., 2018). PSD95 and SAP102 are membrane associated guanylate kinases (MAGUKs) which associate with NMDARs, typically we observe SAP102 at early synapses whereas PSD95 increases later during adolescence indicating more mature synapses. Using deep learning brain alignment tools, ABBA and DeepSlice, we compared SAP102 and PSD95 from early adolescence (P25) to adulthood (P55) illustrating region specific differences. One prominent example is the cortex-wide increase of PSD95 labelling in layer 1 of the neocortex during adolescence. Layer 1 is an important site of integration for top-down inputs that help regulate numerous higher cognitive capabilities, potentially highlighting a key locus underlying adolescent improvements in cognitive functions.