Voltage-Imaging and Simulation of Effects of Voltage- and Agonist- Activated Conductances on Soma-Dendritic Voltage Coupling

Abstract. We investigated the spread of membrane voltage changes from the soma into the dendrites of cerebellar Purkinje cells by using voltage-imaging techniques in combination with intracellular recordings and by performing computer simulations using a detailed compartmental model of a cerebellar Purkinje cell. Fluorescence signals from single Purkinje cells in cerebellar cultures tained with the styryl dye di-4-ANEPPS were detected with a 10 x 10 photodiode array and a charge coupled evice (CCD). Fluorescence intensity decreased and increased with membrane depolarization a d hyperpolarization, respectively. The relation between fractional fluorescence hange (AF/F) and membrane potential could be described by a linear function with a slope of up to-3%/100 inV. Hyperpolarizing and depolarizing voltage jumps applied to Purkinje cells voltage-clamped with an intrasomatic recording electrode induced endritic dye signals, demonstrating that these voltage transients invaded the dendrites. Dye signals induced by depolarizing somatic voltage jumps were weaker in the dendrites, when compared with those induced by hyperpolarizing voltage jumps. Dendritic responses tohyperpolarizing voltage steps applied at the soma were attenuated when membrane conductance was increased by muscimol, an agonist for GABAA receptors. Corresponding experimental protocols were applied to a previously developed etailed compartmental model of a Purkinje cell. In the model, as in the electrophysiological recordings, voltage attenuation from soma to dendrites increased under conditions where membrane conductance is increased by depolarization rby activation of GABA