γ-Aminobutyric Acid and Glutamate Differentially Regulate Intracellular Calcium Concentrations in Mouse Gonadotropin-Releasing Hormone Neurons

Abstract

Multiple factors regulate the activity of the GnRH neurons responsible for controlling fertility. Foremost among neuronal inputs to GnRH neurons are those using the amino acids glutamate and gamma-aminobutyric acid (GABA). The present study used a GnRH-Pericam transgenic mouse line, enabling live cell imaging of intracellular calcium concentrations ([Ca(2+)](i)) to evaluate the effects of glutamate and GABA signaling on [Ca(2+)](i) in peripubertal and adult mouse GnRH neurons. Activation of GABA(A), N-methyl-d-aspartate, or alpha-amino-3-hydroxyl-5-methyl-4-isoxazole propionate acid (AMPA) receptors was found to evoke an increase in [Ca(2+)](i), in subpopulations of GnRH neurons. Approximately 70% of GnRH neurons responded to GABA, regardless of postnatal age or sex. Many fewer (approximately 20%) GnRH neurons responded to N-methyl-d-aspartate, and this was not influenced by postnatal age or sex. In contrast, about 65% of adult male and female GnRH neurons responded to AMPA compared with about 14% of male and female peripubertal mice (P < 0.05). The mechanisms underlying the ability of GABA and AMPA to increase [Ca(2+)](i) in adult GnRH neurons were evaluated pharmacologically. Both GABA and AMPA were found to evoke [Ca(2+)](i) increases through a calcium-induced calcium release mechanism involving internal calcium stores and inositol-1,4,5-trisphosphate receptors. For GABA, the initial increase in [Ca(2+)](i) originated from GABA(A) receptor-mediated activation of L-type voltage-gated calcium channels, whereas for AMPA this appeared to involve direct calcium entry through the AMPA receptor. These observations show that all of the principal amino acid receptors are able to control [Ca(2+)](i) in GnRH neurons but that they do so in a postnatal age- and intracellular pathway-specific manner.

Frequency-Dependent Recruitment of Fast Amino Acid and Slow Neuropeptide Neurotransmitter Release Controls Gonadotropin-Releasing Hormone Neuron Excitability

“…Previous studies examining the effects of GABA A receptor activation on adult GnRH neurons have generated conflicting results (DeFazio et al, 2002;Han et al, 2002Han et al, , 2004Moenter and DeFazio, 2005), and the reasons for this discrepancy have not been resolved. Interestingly, recent investigations (Watanabe et al, 2009;Constantin et al, 2010) have reported likely depolarizing effects of GABA A receptor activation when examining intracellular calcium concentrations in adult GnRH neurons. One concern in all of these studies is that exogenous GABA is applied as an unphysiological bolus to GnRH neurons.…”

Initiation and Propagation of Action Potentials in Gonadotropin-Releasing Hormone Neuron Dendrites

“…؉ spikes evoke faithful Ca 2؉ transients in the dendrites of GnRH neurons Several previous studies have investigated the effects of activity on Ca 2ϩ signaling in the soma of adult GnRH neurons (Jasoni et al, 2007;Constantin et al, 2010;Lee et al, 2010). However, the effect of spiking in the dendrite has not been determined.…”

Gas release-based prescreening combined with reversed-phase HPLC quantitation for efficient selection of high-γ-aminobutyric acid (GABA)-producing lactic acid bacteria

“…Both GABA and GABA-rich foods have shown antianxiety and antidepressant activities (Krystal et al, 2002;Cryan and Kaupmann, 2005;Chuang et al, 2011), antihypertensive effects Inoue et al, 2003;Yoshimura et al, 2010;Liu et al, 2011), and regulation of hormone secretion (Gamel-Didelon et al, 2002;Constantin et al, 2010). In China and Japan, generally recognized as safe (GRAS)-grade GABA has been approved as a functional food additive.…”