Organization of Activity of Hippocampal Pyramidal Neurons under Coactivation of Dendritic Glutamate- and GABA-Sensitive Receptors: a Simulation Study

Abstract

Using the model of a hippocampal pyramidal neuron with reconstructed dendritic arborization having active electrical properties of the membrane, we investigated the effects of tonic activation of dendritic receptor channels sensitive to glutamate and GABA on the patterns of impulse activity in the axon and on the corresponding electrical processes in the dendrites. Activation of these types of receptors was represented by introducing the uniformly distributed membrane conductivities G se and G si associated with the current reversal potentials of 0 and -60 mV, respectively. It was found that the dendritic membrane with voltage-gated ion channels typical of this-type neurons became, under the influence of suprathreshold activation of glutamate receptors, a source of self-oscillations of the membrane potential or persistent depolarization of the membrane with characteristic differences of the electrical processes in metrically asymmetrical parts of the dendritic arborization. At the neuronal output, regular periodic or stochastic sequences of action potentials (APs) were generated; their average repetition frequency f depended logarithmically on the G se. Coactivation of GABA receptors (G si > 0) led to an increase in the threshold and a decrease in the frequency of auto-oscillations in the dendrites (in this case, the autooscillations were renewed in the branches where persistent depolarization developed previously), as well as to a decrease in the mean frequency of AP firing, whereas the logarithmic dependence of f on the G se remained. An earlier undescribed effect was revealed; the transformation of firing patterns (irregular, stochastic, and regular, periodic) at certain ratios of the conductivities G se and G si occurred. It is assumed that the above-described features of the firing pattern formation in hippocampal pyramidal neurons are due to dynamical spatial coupling of the local auto-oscillatory processes. This coupling depends on the geometry and membrane conductivities of the dendrites, is modulated by coactivation of receptors of different types, and is determined by the parametric sensitivity of the dendritic transfer functions.