COMPARTMENTAL-MODELS OF TYPE-A AND TYPE-B GUINEA-PIG MEDIAL VESTIBULAR NEURONS

1. We have developed compartmental models of guinea-pig medial vestibu lar nuclei neurons (MVNns). The structure and the parameters of the mo del cells were chosen to reproduce the responses of type A and type B MVNns as described in electrophysiologicaI recordings. 2. Dynamics ofm embrane potentials were modeled in 46 and 61 branched electrical compa rtments for Type A and Type B MVNns, respectively. Each compartment wa s allowed to contain up to nine active ionic conductances: a fast inac tivating sodium conductance, g(Na), a persistent sodium conductance, g (Nap), a low-voltage activated calcium conductance, g(Ca(LVA)), a high -voltage activated calcium conductance, g(Ca(HVA)), a fast-voltage act ivated potassium conductance, g(K(fast)), a slowly relaxing Voltage ac tivated potassium conductance, g(K(slow)), a fast transient potassium channel, g(K(A)), a slowly relaxing mixed sodium-potassium conductance activating at hyperpolarized membrane potentials, g(H), and a calcium -activated potassium conductance g(K(AHP)). The kinetics of these cond uctances were derived from voltage-clamp studies in a variety of prepa rations. Kinetic parameters as well as distribution and density of ion channels were adjusted to yield the reported electrophysiological beh avior of medial vestibular neurons. 3. Dynamics of intracellular free [Ca2+](i) were modeled by inclusion of a Ca2+-pump and a Na+-Ca2+ exch anger for extrusion of calcium. Diffusion of calcium between submembra neous sites and the center of an electrical compartment was modeled by 25 and 6 shelf-like chemical compartments for the cell body and the p roximal dendrites, respectively. These compartments also contained bin ding sites for calcium. 4. The dynamics of active conductances were th e same in both models except for g(K(fast)). This was necessary to ach ieve the different shape of spikes and of spike afterhyperpolarization in type A and type B MVNns. An intermediate depolarizing component of the spike afterhyperpolarization of type B neurons in part depended o n their dendritic cable structure. 5. Variation of the low threshold c alcium conductance, g(Ca(LVA)), shows that the ability to generate low -threshold spike bursts critically depends on the density of this cond uctance. Sodium plateaus were generated when increasing the density of g(Nap). 6. The type B model cell generated rhythmic bursts of spiking activity under simulation of two distinct experimental conditions. Th e first experimental condition was the inclusion in the dendritic comp artments of a voltage-dependent conductance with properties replicatin g tonic activation of N-methyl-D-aspartate (NMDA)-type of glutamate re ceptors. The second paradigm was the reduction of the density of g(K(A HP)). The emergence of oscillatory firing under these two specific exp erimental conditions is consistent with electrophysiological recording s not used during construction of the model. We, therefore, suggest th at these models have a high predictive value.