Extracellular DC electric fields induce nonuniform membrane polarization in rat hippocampal CA1 pyramidal neurons

Non-synaptic interactions among neurons via extracellular electric fields may play functional roles in the CNS. Previously in a study using voltage-sensitive dye imaging, we reported characteristic membrane polarization profiles in the CA1 region of hippocampal slices during exposure to extracellular DC fields: slow monophasic polarization in somatic region and biphasic polarization (fast polarization and following slow repolarization) in mid-dendritic region. Here, using optical imaging and patch-clamp recordings, we showed that CA1 pyramidal neurons indeed show the characteristic polarization in response to DC fields, and investigated the mechanism underlying the profiles. Both the monophasic and biphasic polarization could be fitted with a double exponential function. The τs (ms) were 12.6 ± 2.5 and 56.0 ± 4.7 for the monophasic polarization, and 14.2 ± 1.2 and 42.2 ± 2.8 for the biphasic polarization. Based on our previous theoretical studies, we hypothesized that lower resistivity in the distal apical dendrites is responsible for generating the characteristic polarization profiles. We tested this hypothesis by removing the distal apical dendrites or by blocking ion channel-mediated conductance. Removal of distal dendrites caused drastic changes in the polarization profiles, e.g. biphasic polarization was damped. However, none of the blockers tested had a marked effect on the biphasic polarization. Our results demonstrate the importance of the apical dendrite for generating the characteristic polarization profiles, and suggest that voltage-activated conductance, including HCN channel-mediated conductance, had only minor contributions to these profiles. These findings provide a better understanding of how neurons in the CNS respond to extracellular electric fields.

Research highlights
► Extracellular DC fields induce membrane polarization in CA1 pyramidal neurons.
► The polarization profile is spatially and temporally nonuniform along the cell.
► Presence of the distal apical dendrites is important for the nonuniform profile.
► Dendritic ion channels have little contribution to the nonuniform profile.