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A dendrite-resolved, in vivo transfer function from spike patterns to dendritic Ca2+ | bioRxiv

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Dendrites transform local electrical activity into intracellular Ca2+ signals that drive plasticity[1][1],[2][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. ### Competing Interest Statement AEC is a consultant to Quiver Biosciences and to Exin Therapeutics, and is a founder of Luminos LLC. LDL is a scientific cofounder, shareholder, and consultant of Eikon Therapeutics. US Patent 9,933,417 describing azetidine-containing fluorophores and variant compositions (with inventor LDL) is assigned to HHMI. All other authors declare no competing interests. National Research Foundation of Korea, RS-2023-00248959 National Institutes of Health, https://ror.org/01cwqze88, R01-NS126043, R01-NS133755, R01-MH117042 Chan Zuckerberg Initiative (United States), 2023-321177 Office of Naval Research, N00014-18-1-2859 Howard Hughes Medical Institute, https://ror.org/006w34k90 [1]: #ref-1 [2]: #ref-2

New Results , Byung Hun Lee, Pojeong Park, J. David Wong-Campos, Junjie Xu, Sarah E. Plutkis, View ORCID ProfileLuke D. Lavis, View ORCID ProfileAdam E. Cohen doi: https://doi.org/10.64898/2026.01.18.700189 Abstract Dendrites transform local electrical activity into intracellular Ca2+ signals that drive plasticity1,2, 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…

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