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.

Synaptic Regulation of Proopiomelanocortin Neurons Can Occur Distal to the Arcuate Nucleus

“…These data suggest that the interactions within the hypothalamus are not only regulated by axons projecting to target structures but also by inputs that terminate outside of the nucleus containing the cell bodies. Far-reaching dendrites have recently been described in other hypothalamic neurons (Roberts et al 2006), indicating that regulation of neuron activity occurring at distal sites may be common in the hypothalamus.…”

A simple integrative electrophysiological model of bursting GnRH neurons

“…Considering earlier results that underline the importance of dendritic mechanisms in the case of GnRH neurons (Campbell et al, 2009;Roberts et al, 2006;Roberts, Hemond, & Suter, 2008) which may contribute to the description of AP generation (Roberts, Campbell, et al, 2008), bursting (Izhikevich, 2005) and DAPs (Roberts et al, 2009), we take into account an active dendritic compartment. Furthermore, because the majority of our measurement data originates from bipolar GnRH neurons, a second, passive dendritic compartment is also incorporated in the model.…”

“…This aim was fulfilled with the application of a simplified model for the description of AP generation, which reduced the model complexity compared to previous results Duan et al, 2011) regarding the models of GnRH neuronal bursting. In addition, the proposed model is capable of the description of depolarizing afterpotentials, simple somato-dendritic interactions (see (Roberts et al, 2006;Roberts, Hemond, & Suter, 2008;Roberts et al, 2009)), and approximated reproduction of the shape of single APs. Furthermore, during model development, the parameters of the voltage dependent calcium current were determined according to (Kato et al, 2003).…”

“…A couple of models have been constructed so far to describe the ionic currents and short term (considering scales of milliseconds) general electrophysiological (Csercsik et al, 2010), and dendritic properties (Roberts et al, 2006;Roberts, Hemond, & Suter, 2008;Roberts et al, 2009) of GnRH neurons based on measurements performed on cells from hypothalamic slices. Other mathematical models (LeBeau *Manuscript Click here to download Manuscript: GnRH_neuron_RR_2_bbl.tex Click here to view linked References 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 2 et Van Goor et al, 2000;Fletcher & Li, 2009) have been proposed to explain experimental data obtained on GT1 cells.…”

Synaptic integration in hypothalamic gonadotropin releasing hormone (GnRH) neurons

“…Somata contained Fast Na + , Delayed Rectifier K + (Kusano et al, 1995) and Inward Rectifier K + (Kusano et al, 1995;Wagner et al, 1998), and L-type Ca 2+ conductances (Kusano et al, 1995;Spergel 2007). Fast Na + and Delayed Rectifier K + conductances were incorporated in dendrites and axons.The first, passive dendrite versions of our models have been published elsewhere (Roberts et al, 2006). The model in this study used the branching GnRH neuron morphology from the previous model, and was tuned to the same passive and active measured electrophysiology.…”