Heterogeneity in the Basic Membrane Properties of Postnatal Gonadotropin-Releasing Hormone Neurons in the Mouse

Abstract

The electrophysiological characteristics of unmodified, postnatal gonadotropin-releasing hormone (GnRH) neurons in the female mouse were studied using whole-cell recordings and single-cell RT-PCR methodology. The GnRH neurons of adult animals fired action potentials and exhibited distinguishable voltage-current relationships in response to hyperpolarizing and depolarizing current injections. On the basis of their patterns of inward rectification, rebound depolarization, and ability to fire repetitively, GnRH neurons in intact adult females were categorized into four cell types (type I, 48%; type II, 36%; type III, 11%; type IV, 5%). The GnRH neurons of juvenile animals (15-22 d) exhibited passive membrane properties similar to those of adult GnRH neurons, although only type I (61%) and type II (7%) cells were encountered, in addition to a group of "silent-type" GnRH neurons (32%) that were unable to fire action potentials. A massive, action potential-independent tonic GABA input, signaling through the GABA A receptor, was present at all ages. Afterdepolarization and afterhyperpolarization potentials (AHPs) were observed after single action potentials in subpopulations of each GnRH neuron type. Tetrodotoxin (TTX)-independent calcium spikes, as well as AHPs, were encountered more frequently in juvenile GnRH neurons compared with adults. These observations demonstrate the existence of multiple layers of functional heterogeneity in the firing properties of GnRH neurons. Together with pharmacological experiments, these findings suggest that potassium and calcium channels are expressed in a differential manner within the GnRH phenotype. This heterogeneity occurs in a development-specific manner and may underlie the functional maturation and diversity of this unique neuronal phenotype.

Estrogen Receptor β Mediates Rapid Estrogen Actions on Gonadotropin-Releasing Hormone NeuronsIn Vivo

“…Such a scenario would be in good agreement with evidence for the expression of ER␤, but not ER␣, in GnRH neurons (Herbison and Pape, 2001). A common theme in the investigation of the GnRH neuronal phenotype is that of marked heterogeneity (Sim et al, 2001), and once again, we find here that only a subpopulation (25-40%) of all GnRH neurons, irrespective of location, respond to estrogen. Studies in mice have shown that ϳ20% of adult female GnRH neurons express ER␤ transcripts , whereas work in the rat has demonstrated 50 -80% of GnRH neurons to contain ER␤ immunoreactivity (Hrabovszky et al, 2001;Kallo et al, 2001).…”

Effects of GABA and Bicuculline on the Electrical Activity of Rat Olfactory Placode Neurons Derived at E13.5 and Cultured for 1 Week on Multi-electrode Dishes

“…These frequencies were almost similar to those for mouse GnRH neurons; in GnRH neurons derived from 11.5-day-old mouse embryos and cultured for 1-2 weeks, the frequencies of spontaneous firing rate were smaller than 4 Hz [15], and in single GnRH neurons derived from 15-20-day-old mice, the frequencies were 0.02-1.0 Hz (0.4 ± 0.1 Hz) [21,22]. Although we did not determine in the present study whether the recorded neurons were GnRH neurons or not, it is likely that each activity was recorded from 1 or at most 2 neurons.…”

Two Slow Calcium-Activated Afterhyperpolarization Currents Control Burst Firing Dynamics in Gonadotropin-Releasing Hormone Neurons

“…All drugs (Tocris Biosciences) were applied to the ACSF bathing solution at the following established concentrations: apamin 300 nM (Liu and Herbison, 2008), UCL2077 10 M (Shah et al, 2006), 2-aminoethoxydiphenylborate (2-APB) 100 M (Jasoni et al, 2007), cyclopiazonic acid (CPA) 30 M (Power and Sah, 2008) and tetrodotoxin (TTX) 0.5 M (Sim et al, 2001). Apamin and TTX were dissolved in water while the others were dissolved initially in dimethylsulfoxide resulting in a final dimethylsulfoxide concentration in the perfusion solution of 0.03 to 0.1%.…”