Compartmental models of type A and type B guinea pig medial vestibular neurons

1. We have developed compartmental models of guinea-pig medial vestibular nuclei neurons (MVNns). The structure and the parameters of the model cells were chosen to reproduce the responses of type A and type B MVNns as described in electrophysiological recordings. 2. Dynamics of membrane potentials were modeled in 46 and 61 branched electrical compartments for Type A and Type B MVNns, respectively. Each compartment was allowed to contain up to nine active ionic conductances: a fast inactivating 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 activated potassium conductance, g(K(fast)), a slowly relaxing voltage activated 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 conductances were derived from voltage-clamp studies in a variety of preparations. Kinetic parameters as well as distribution and density of ion channels were adjusted to yield the reported electrophysiological behavior of medial vestibular neurons. 3. Dynamics of intracellular free [Ca²⁺](i) were modeled by inclusion of a Ca²⁺-pump and a Na⁺-Ca²⁺ exchanger for extrusion of calcium. Diffusion of calcium between submembraneous sites and the center of an electrical compartment was modeled by 25 and 6 shell-like chemical compartments for the cell body and the proximal dendrites, respectively. These compartments also contained binding sites for calcium. 4. The dynamics of active conductances were the same in both models except for g(K(fast)). This was necessary to achieve 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 on their dendritic cable structure. 5. Variation of the low threshold calcium conductance, g(Ca(LVA)), shows that the ability to generate low-threshold spike bursts critically depends on the density of this conductance. 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. The first experimental condition was the inclusion in the dendritic compartments of a voltage-dependent conductance with properties replicating tonic activation of N-methyl-D-aspartate (NMDA)- type of glutamate receptors. The second paradigm was the reduction of the density of g(K(AHP)). The emergence of oscillatory firing under these two specific experimental conditions is consistent with electrophysiological recordings not used during construction of the model. We, therefore, suggest that these models have a high predictive value.