Clustered inputs engage dendritic nonlinearities and calcium signaling to support efficient place-field formation in...

How the spatial arrangement of synaptic inputs shapes neuronal feature selectivity remains a fundamental question. Here, we map the three-dimensional distribution of excitatory and inhibitory synapses across the dendritic arbor of CA1 pyramidal neurons in vivo and build biophysical models to probe their impact on place-cell emergence. Excitatory synapses are non-uniformly distributed, forming structural clusters preferentially on terminal apical and basal dendrites, whereas inhibitory synapses are uniformly arranged. Relative to dispersed configurations, clustered inputs generate higher-quality, stable place fields while recruiting ∼13% fewer active synapses for equivalent somatic output, and cause elevated voltage-gated calcium influx and NMDA-receptor activation. Notably, disrupting clustering permits recovery of somatic excitability but not dendritic calcium dynamics, implicating clustering in calcium-dependent plasticity. Synaptic organization further determines integration strategy: clustered inputs preferentially engage apical dendritic nonlinearities, whereas distributed inputs rely on basal summation. These results establish synaptic clustering as a core mechanism for efficient, compartmentalized spatial computation.