LOSS OF PSD-95 LEADS TO DISTURBED BINOCULAR PROCESSING IN MOUSE PRIMARY VISUAL CORTEX (V1)

Postsynaptic density protein 95 (PSD-95) is an important signalling scaffold of the PSD of excitatory synapses. We have previously shown that PSD-95 dependent silent synapse maturation closes the critical period (CP) for ocular dominance plasticity in mouse V1, and is needed for proper synapse stabilization. Behaviourally, PSD-95 KO mice exhibit impaired binocular predation and orientation discrimination but improve with monocular vision. Since binocularity and binocular matching of orientation preference develops during the CP, we hypothesized that PSD-95 KO mice should display compromised binocular integration. To this end, we recorded monocular/binocular visual responses using 2-photon Calcium-imaging (AAV9.Syn.GCaMP6s.WPRE.SV40, Resonant-Galvo scanner, 30.06/15.62 Hz bi/unidirectional) in L2/3 V1-neurons of adult (~P127-260) awake PSD-95 KO/WT mice. Neuronal firing rates to visual stimuli presented binocularly, and monocularly to both ipsi- and contralateral eyes (based on Tan et al. 2020, JNS 42:3546, 2/4Hz flashing sinusoidal static gratings, 18 orientations, 3 phases, 8/10 spatial frequencies with 4/6 repetitions) were estimated through spike deconvolution with the CaImAn toolbox. Compared to WT, KO binocular neurons exhibited a greater contralateral dominance (ODI calculated by firing rate, KO/WT 0.23±0.02/0.07±0.02, p<0.001), a decrease in %neurons with significant correlation of the eyes’ orientation x spatial frequency tuning matrices (KO/WT 12%/52%, p<0.001). Notably, there was also a greater binocular mismatch of preferred orientation in binocular V1-neurons (KO/WT 41°±3°/27°±2°, p<0.001). Together, our data strongly support a role of experience-dependent silent synapse maturation for the refinement of cortical circuitry for proper binocular signal processing in mouse V1.