A dendrite-resolved, <i>in vivo</i> transfer function from spike patterns to dendritic Ca ²⁺

Dendrites transform local electrical activity into intracellular Ca²⁺ signals that drive plasticity^1,2, yet the voltage→Ca²⁺ mapping during natural behavior remains poorly defined. Here, we measure this transfer function via simultaneous voltage and Ca²⁺ imaging throughout the dendritic arbors of hippocampal CA2 pyramidal neurons in behaving mice. Dendritic Ca²⁺ exhibited a hierarchical activation pattern dominated by back-propagating action potentials: simple spikes primarily drove somatic and proximal Ca²⁺, whereas complex spikes produced larger somatic Ca²⁺ signals and propagated farther into distal dendrites, sometimes in a branch-selective manner. Dendrite-restricted co-activation of voltage and Ca²⁺ without concurrent somatic events was rare. A biophysics-inspired model accurately predicted local Ca²⁺ transients from local voltage waveforms. Our data and model provide a quantitative understanding of when - and why - dendritic Ca²⁺ signals in CA2 pyramidal cells arise during behavior.