ENHANCING OUTPUT SYNAPSES OF CA1 HIPPOCAMPAL PYRAMIDAL NEURONS THROUGH INCREASED VESICLE PRIMING DOES NOT ALTER THEIR SPATIAL TUNING

The spatial tuning of spiking of pyramidal cells in the CA1 area of the dorsal hippocampus (CA1PCs) is essential for spatial learning and navigation. CA1PCs innervate local GABAergic interneurons (INs), which in turn regulate their activity, with specialized synapses. Synapses made onto fast-spiking INs, show high vesicle release probability (Pv) and short-term depression. In contrast, synapses made onto O-LM INs, show low Pv and short-term facilitation. This specialization in synaptic transmission is realized through differential synaptic vesicle priming by Munc13-1. How this cell type-specific input from CA1PCs to GABAergic INs contributes to spatial tuning of CA1PCs is unknown. To investigate this, we recorded the activity of GCamp8s expressing CA1PCs using 2-photon calcium-imaging in head-fixed mice running on a belt in virtual reality. We induced a gain-of-function mutation in the C1 domain (H576K) of Munc13-1 specifically in CA1PCs, resulting in a 7-fold and a 50% increase in Pv at synapses onto O-LM and fast-spiking INs, respectively. The fraction of place cells (cells with significant spatial tuning) was variable but was not different between animals carrying the point-mutation and wild-type controls. The width of place fields was also similar between groups. Furthermore, correlations of spatial tuning curves and lap-by-lap population vector correlations of CA1PCs showed similar stability and specificity of spatial representations across days and in distinct virtual environments between mutants and controls. We conclude that enhancing output synapses of CA1PCs, particularly those made onto O-LM INs, is not sufficient to alter their spatial tuning during navigation in a linear virtual environment.