Dendritic voltage imaging reveals biophysical basis of associative plasticity rules

Dendrites on neurons integrate synaptic inputs to determine spike timing. Dendrites also convey back-propagating action potentials (bAPs), where these signals interact with synaptic inputs to strengthen or weaken individual synapses. To study dendritic integration and associative plasticity rules, we developed molecular, optical, and computational tools for all-optical electrophysiology in dendrites. We mapped sub-millisecond voltage dynamics throughout the dendritic trees of CA1 pyramidal neurons in acute brain slices. Our data show history-dependent bAP propagation in distal dendrites, driven by locally generated Na(+) spikes (dSpikes). Dendritic depolarization led to a transient window for dSpike propagation, opened by A-type K(V) channel inactivation, and closed by slow Na(V) inactivation. Collisions of dSpikes with synaptic inputs triggered N-methyl-D-aspartate receptor (NMDAR)-dependent plateau potentials. These results, combined with numerical simulations, paint an intuitive picture connecting dendritic biophysics to associative plasticity rules.