Dendritic processing of excitatory synaptic input in hypothalamic gonadotropin releasing-hormone neurons

Abstract

The activity of hypothalamic GnRH neurons results in the intermittent release of GnRH required for reproductive function. This intermittent neurosecretory activity has been proposed to reflect integration of intrinsic properties of and synaptic input to GnRH neurons. Determining the relative impact of synaptic inputs at different locations on the GnRH neuron is difficult, if not impossible, using only experimental approaches. Thus, we used electrophysiological recordings and neuronal reconstructions to generate computer models of GnRH neurons to examine the effects of synaptic inputs at varying distances from the soma along dendrites. The parameters of the models were adjusted to duplicate measured passive and active electrophysiology of cells from mouse brain slices. Our morphological findings reinforce the emerging picture of a complex dendritic structure of GnRH neurons. Furthermore, analysis of reduced morphology models indicated that this population of cells is unlikely to exhibit low-frequency tonic spiking in the absence of synaptic input. Finally, applying realistic patterns of synaptic input to modeled GnRH neurons indicates that synapses located more than about 30% of the average dendrite length from the soma cannot drive firing at frequencies consistent with neuropeptide release. Thus, processing of synaptic input to dendrites of GnRH neurons is probably more complex than simple summation.