Fast dendritic excitations primarily mediate back-propagation in CA1 pyramidal neurons during behavior

Abstract Dendrites integrate synaptic inputs to trigger action potentials, and dendrites carry back-propagating action potentials (bAPs) to synapses where these signals contribute to plasticity. Despite strong evidence for a rich repertoire of nonlinear dendritic excitations, the in vivo roles of these excitations in dendritic integration and back-propagation remain uncertain. Here, we used high-speed voltage imaging through a chronically implanted microprism to map membrane potential dynamics from basal to apical dendrites of CA1 neurons in mice navigating in a virtual reality environment. Despite complex dendritic branch morphology, the dynamics were largely captured by 2 or 3 electrical compartments: basal, soma, and apical. Fast dendritic spikes almost always started from bAPs, indicating that dendritic spikes are primarily a consequence rather than a cause of somatic spiking. These fast spikes sometimes triggered slower apical dendritic plateau depolarizations, which drove complex spikes at the soma. We found that the biophysics of dendritic excitability determined the distribution of simple and complex spikes across a place field. Our results show how CA1 pyramidal neurons convert synaptic inputs to spiking outputs and suggest a primary role of dendritic nonlinearities in mediating activity-dependent plasticity. 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.