Dendrites determine the contribution of after depolarization potentials (ADPs) to generation of repetitive action potentials in hypothalamic gonadotropin releasing-hormone (GnRH) neurons

Abstract

The impact of structure in modulating synaptic signals originating in dendrites is widely recognized. In this study, we focused on the impact of dendrite morphology on a local spike generating mechanism which has been implicated in hormone secretion, the after depolarization potential (ADP). Using multi-compartmental models of hypothalamic GnRH neurons, we systematically truncated dendrite length and determined the consequence on ADP amplitude and repetitive firing. Decreasing the length of the dendrite significantly increased the amplitude of the ADP and increased repetitive firing. These effects were observed in dendrites both with and without active conductances suggesting they largely reflect passive characteristics of the dendrite. In order to test the findings of the model, we performed whole-cell recordings in GnRH neurons and elicited ADPs using current injection. During recordings, neurons were filled with biocytin so that we could determine dendritic and total projection (dendrite plus axon) length. Neurons exhibited ADPs and increasing ADP amplitude was associated with decreasing dendrite length, in keeping with the predictions of the models. Thus, despite the relatively simple morphology of the GnRH neuron's dendrite, it can still exert a substantial impact on the final neuronal output.

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 will allow us to study the somato-dendritic interactions in the model, without the needs for more complex spatial models and morphological considerations (see eg. (Roberts et al, 2009) (Izhikevich, 2005), to describe action potential generation, we use the following impulsive system (Bainov & Simeonov, 1989) for the characterization of the membrane potential and voltage gated inactivation currents for the somatic compartment…”

“…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.…”

Dual Somatic Recordings from Gonadotropin-Releasing Hormone (GnRH) Neurons Identified by Green Fluorescent Protein (GFP) in Hypothalamic Slices

“…Hypothalamic brain slices are prepared, incubated and transferred to the recording chamber as previously detailed (9) in animals whose GnRH neurons express green fluorescent protein (GFP) under the control of the GnRH peptide promoter (10). After removal of the brain from the animal, the brain is blocked using a razor blade to eliminate regions that are not of interest.…”