From Morphology to Computation: How Synaptic Organization Shapes Place Fields in CA1 Pyramidal Neurons.

The synaptic mechanisms driving feature selectivity in specific neuron types remains a fundamental and unresolved challenge in neuroscience. In hippocampal CA1 pyramidal neurons (PNs), the development of place selectivity, manifested as place fields, is believed to result from dendritic integration of spatially distributed inputs combined with behavioral time scale plasticity (BTSP). BTSP involves dendritic spikes that temporally regulate synaptic potentiation and depotentiation. However, the role of excitatory (E) and inhibitory (I) synaptic distributions in the emergence of place specificity in CA1 PNs remains unclear, due to the lack of detailed synaptic reconstructions in vivo. Here, we present full synaptic reconstructions from individual CA1 PNs in the mouse hippocampus, revealing that these neurons receive approximately 10,000-15,000 E synapses and 900-1,400 I synapses. Computational modeling of biologically relevant E and I synaptic distributions shows that spatial tuning is preserved with co-tuned, spatially clustered E synapses, but disrupted when E distributions are randomized. Moreover, synapse clustering has a different contribution to spatial tuning in apical vs. basal domains. Our results reveal a complex and finely-tuned interplay between presynaptic input patterns and the spatial organization of their postsynaptic targets in dictating neuronal output in CA1 PNs.