scholarly journals Endogenous γ-Aminobutyric Acid Can Excite Gonadotropin-Releasing Hormone Neurons

Endocrinology ◽  
2005 ◽  
Vol 146 (12) ◽  
pp. 5374-5379 ◽  
Author(s):  
Suzanne M. Moenter ◽  
R. Anthony DeFazio
Keyword(s):  
Firing Rate ◽  
Brain Slices ◽  
Aminobutyric Acid ◽  
Firing Activity ◽  
Action Potential Firing ◽  
Neuron Response ◽  
Gnrh Neurons ◽  
Potential Firing ◽  
Gaba Transmission

γ-Aminobutyric acid (GABA) provides a major synaptic input to GnRH neurons. GnRH neurons maintain high intracellular chloride levels and respond to exogenous GABA with depolarization and action potential firing. We examined the role of synaptic GABA type A receptor (GABAAR) activation on the firing activity of GnRH neurons. Targeted extracellular recordings were used to detect firing activity of GnRH neurons in brain slices from adult female mice. Because the brain slice preparation preserves both glutamatergic and GABAergic neuronal networks, the effects of GABAARs on GnRH neurons were isolated by blocking ionotropic glutamatergic receptors (iGluR). With iGluR blocked, many GnRH neurons remained spontaneously active. Consistent with an excitatory role for GABA, subsequent blockade of GABAARs suppressed the firing rate in active cells from diestrous females by approximately 40% (P < 0.05; n = 10). GABAAR blockade did not affect inactive cells (n = 7), indicating that GABAAR-mediated inhibition was not responsible for the lack of firing. In prenatally androgenized females, GnRH neurons exhibit larger, more frequent GABAergic postsynaptic currents than control females. Most cells from prenatally androgenized animals fired spontaneously, and the firing rate was suppressed approximately 80% after GABAAR blockade (P < 0.01; n = 8). Blocking GABAAR without blocking iGluRs increased the firing rate in GnRH neurons from diestrous females (P < 0.05; n = 6), perhaps attributable to hyperexcitability within the slice network. Our results indicate that GABAergic inputs help generate a portion of action potentials in GnRH neurons; this fraction depends on the level of GABA transmission and postsynaptic responsiveness. The complexities of the GnRH neuron response to GABA make this a potentially critical integration point for central regulation of fertility.

scholarly journals Androgens Increase Gonadotropin-Releasing Hormone Neuron Firing Activity in Females and Interfere with Progesterone Negative Feedback

Endocrinology ◽  
2006 ◽  
Vol 147 (3) ◽  
pp. 1474-1479 ◽  
Author(s):  
Justyna Pielecka ◽  
Samuel D. Quaynor ◽  
Suzanne M. Moenter
Keyword(s):  
Animal Models ◽  
Firing Rate ◽  
Negative Feedback ◽  
Brain Slices ◽  
Neuron Activity ◽  
Gnrh Neuron ◽  
Firing Activity ◽  
Neuron Firing ◽  
Gnrh Neurons ◽  
Gaba Transmission

GnRH neurons are the central regulators of fertility, and their activity is modulated by steroid feedback. In women with hyperandrogenemic infertility and in animal models of these disorders, elevated androgen levels interfere with progesterone (P) negative feedback. Our previous work showed that steroids altered the frequency and amplitude of γ-aminobutyric acid (GABA) transmission to GnRH neurons. Specifically, P inhibited GABA transmission, which can excite GnRH neurons, whereas dihydrotestosterone (DHT) increased GABA transmission. In this study the GnRH neuron firing rate was examined in the same animal models. Adult (>2 months) female mice were ovariectomized and treated for 8–12 d with implants containing estradiol (E), E and P, E and DHT, or E, P, and DHT. Targeted extracellular recordings were used to examine the long-term firing activity of green fluorescent protein-identified GnRH neurons in brain slices from these mice. In comparing E alone to E plus P animals, P increased the percentage of time that GnRH neurons were quiescent and reduced the area under the curve of the firing rate and the instantaneous firing frequency, suggesting that P provides additional negative feedback over E alone. The addition of DHT markedly increased GnRH neuron activity in both the presence and absence of P. DHT also altered the firing pattern of GnRH neurons, such that peaks in the firing rate detected by the Cluster8 algorithm were approximately doubled in frequency and amplitude. These data support and extend our previous findings and are consistent with the hypothesis that the changes in GABAergic transmission observed in these animal models impact upon the activity of GnRH neurons, and central androgen action probably stimulates GnRH release.

scholarly journals Slc38a1 Conveys Astroglia-Derived Glutamine into GABAergic Interneurons for Neurotransmitter GABA Synthesis

Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1686
Author(s):  
Tayyaba Qureshi ◽  
Mona Bjørkmo ◽  
Kaja Nordengen ◽  
Vidar Gundersen ◽  
Tor Paaske Utheim ◽  
...  
Keyword(s):  
Neuronal Development ◽  
Brain Slices ◽  
Gabaergic Neurons ◽  
Action Potential Firing ◽  
Wide Range ◽  
Gaba Signaling ◽  
Potential Firing ◽  
Gaba Synthesis ◽  
Neuronal Functions

GABA signaling is involved in a wide range of neuronal functions, such as synchronization of action potential firing, synaptic plasticity and neuronal development. Sustained GABA signaling requires efficient mechanisms for the replenishment of the neurotransmitter pool of GABA. The prevailing theory is that exocytotically released GABA may be transported into perisynaptic astroglia and converted to glutamine, which is then shuttled back to the neurons for resynthesis of GABA—i.e., the glutamate/GABA-glutamine (GGG) cycle. However, an unequivocal demonstration of astroglia-to-nerve terminal transport of glutamine and the contribution of astroglia-derived glutamine to neurotransmitter GABA synthesis is lacking. By genetic inactivation of the amino acid transporter Solute carrier 38 member a1 (Slc38a1)—which is enriched on parvalbumin+ GABAergic neurons—and by intraperitoneal injection of radiolabeled acetate (which is metabolized to glutamine in astroglial cells), we show that Slc38a1 mediates import of astroglia-derived glutamine into GABAergic neurons for synthesis of GABA. In brain slices, we demonstrate the role of Slc38a1 for the uptake of glutamine specifically into GABAergic nerve terminals for the synthesis of GABA depending on demand and glutamine supply. Thus, while leaving room for other pathways, our study demonstrates a key role of Slc38a1 for newly formed GABA, in harmony with the existence of a GGG cycle.

scholarly journals Stabilizing Role of Calcium Store-Dependent Plasma Membrane Calcium Channels in Action-Potential Firing and Intracellular Calcium Oscillations

2005 ◽  
Vol 89 (6) ◽  
pp. 3741-3756 ◽  
Author(s):  
J.M.A.M. Kusters ◽  
M.M. Dernison ◽  
W.P.M. van Meerwijk ◽  
D.L. Ypey ◽  
A.P.R. Theuvenet ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Calcium Channels ◽  
Action Potential ◽  
Intracellular Calcium ◽  
Calcium Oscillations ◽  
Action Potential Firing ◽  
Calcium Store ◽  
Potential Firing

scholarly journals Dose-Dependent Switch in Response of Gonadotropin-Releasing Hormone (GnRH) Neurons to GnRH Mediated through the Type I GnRH Receptor

Endocrinology ◽  
2004 ◽  
Vol 145 (2) ◽  
pp. 728-735 ◽  
Author(s):  
Chun Xu ◽  
Xu-Zhi Xu ◽  
Craig S. Nunemaker ◽  
Suzanne M. Moenter
Keyword(s):  
Firing Rate ◽  
Fluorescent Protein ◽  
Brain Slices ◽  
Dose Dependence ◽  
Gnrh Receptor ◽  
Neuron Activity ◽  
Type I ◽  
Pulsatile Release ◽  
Gnrh Neurons ◽  
Green Fluorescent

Abstract Pulsatile release of GnRH provides central control of reproduction. GnRH neuron activity is likely synchronized to produce hormone pulses, but the mechanisms are largely unknown. One candidate for communication among these neurons is GnRH itself. Cultured embryonic and immortalized GnRH neurons express GnRH receptor type I (GnRHR-1), but expression has not been shown in adult GnRH neurons. Using mice that express green fluorescent protein (GFP) in GnRH neurons, we tested whether adult GnRH neurons express GnRHR-1. GFP-positive (n = 42) and -negative neurons (n = 22) were harvested from brain slices, and single-cell RT-PCR was performed with cell contents. Fifty-two percent of the GnRH neurons tested expressed GnRHR-1, but only 9% of non-GnRH hypothalamic neurons expressed GnRHR-1; no false harvest controls (n = 13) were positive. GnRHR-1 expression within GnRH neurons suggested a physiological ultrashort loop feedback role for GnRH. Thus, we examined the effect of GnRH on the firing rate of GnRH neurons. Low-dose GnRH (20 nm) significantly decreased firing rate in 12 of 22 neurons (by 42 ± 4%, P < 0.05), whereas higher doses increased firing rate (200 nm, five of 10 neurons, 72 ± 26%; 2000 nm, nine of 13 neurons, 53 ± 8%). Interestingly, the fraction of GnRH neurons responding was similar to the fraction in which GnRHR-1 was detected. Together, these data demonstrate that a subpopulation of GnRH neurons express GnRHR-1 and respond to GnRH with altered firing. The dose dependence suggests that this autocrine control of GnRH neurons may be not only a mechanism for generating and modulating pulsatile release, but it may also be involved in the switch between pulse and surge modes of release.

scholarly journals Kisspeptin Increases γ-Aminobutyric Acidergic and Glutamatergic Transmission Directly to Gonadotropin-Releasing Hormone Neurons in an Estradiol-Dependent Manner

Endocrinology ◽  
2010 ◽  
Vol 151 (1) ◽  
pp. 291-300 ◽  
Author(s):  
Justyna Pielecka-Fortuna ◽  
Suzanne M. Moenter
Keyword(s):  
Negative Feedback ◽  
Positive Feedback ◽  
Brain Slices ◽  
Cell Voltage ◽  
Dependent Manner ◽  
Glutamatergic Transmission ◽  
Neuron Response ◽  
Gnrh Neurons ◽  
Gnrh Release ◽  
In Cells

Abstract GnRH neurons are the final central pathway controlling fertility. Kisspeptin potently activates GnRH release via G protein-coupled receptor 54 (GPR54). GnRH neurons express GPR54, and kisspeptin can act directly; however, GPR54 is broadly expressed, suggesting indirect actions are possible. Transsynaptic mechanisms are involved in estradiol-induced potentiation of GnRH neuron response to kisspeptin. To investigate these mechanisms, separate whole-cell voltage-clamp recordings were performed of γ-aminobutyric acid (GABA)-ergic and glutamatergic transmission to GnRH neurons in brain slices before and during kisspeptin treatment. To determine whether estradiol alters the effect of kisspeptin on synaptic transmission, mice were ovariectomized and either left with no further treatment (OVX) or treated with estradiol implants (OVX+E). Cells were first studied in the morning when estradiol exerts negative feedback. Kisspeptin increased frequency and amplitude of GABAergic postsynaptic currents (PSCs) in GnRH neurons from OVX+E mice. Blocking action potentials eliminated the effect on frequency, indicating presynaptic actions. Amplitude changes were due to postsynaptic actions. Kisspeptin also increased frequency of glutamatergic excitatory PSCs in cells from OVX+E animals. Kisspeptin did not affect either GABAergic or glutamatergic transmission to GnRH neurons in cells from OVX mice, indicating effects on transmission are estradiol dependent. In contrast to stimulatory effects on GABAergic PSC frequency during negative feedback, kisspeptin had no effect during positive feedback. These data suggest estradiol enables kisspeptin-mediated increases in GABA and glutamate transmission to GnRH neurons. Furthermore, the occlusion of the response during positive feedback implies one consequence of estradiol positive feedback is an increase in transmission to GnRH neurons mediated by endogenous kisspeptin.

Effects of 5-HT alone and its interaction with TRH on neurons in rat dorsal motor nucleus of the vagus

1995 ◽  
Vol 268 (2) ◽  
pp. G292-G299 ◽  
Author(s):  
R. A. Travagli ◽  
R. A. Gillis
Keyword(s):  
Firing Rate ◽  
Animal Studies ◽  
Motor Nucleus ◽  
Excitatory Effect ◽  
Action Potential Firing ◽  
Patch Clamp Technique ◽  
Dorsal Motor Nucleus ◽  
Potential Firing ◽  
Cell Current

The purpose of this study was to determine whether exposure to thyrotropin-releasing hormone (TRH) enhances the excitatory effect of 5-hydroxytryptamine (5-HT) on motoneurons of the dorsal motor nucleus of the vagus (DMV) as described in whole animal studies. For this purpose we used the patch-clamp technique applied to rat brain stem slices. Exposure of DMV motoneurons to concentrations of 5-HT (0.1-3 microM) resulted in a concentration-related increase in spontaneous firing rate. As previously described by Travagli et al. [Am. J. Physiol. 263 (Gastrointest. Liver Physiol. 26): G508-G517, 1992], TRH (1-30 microM) increased action potential firing rate. Indeed, when TRH perfusion increased the firing rate, addition of 5-HT to the perfusing solution exerted no further excitation of the DMV motoneuron, indicating that there was no summation of response. Studies using whole cell current recordings showed a common action of 5-HT and TRH in antagonizing the Ca(2+)-dependent afterhyperpolarizing current (IAHP). Again, interaction studies between TRH and 5-HT indicated no enhancing effect of TRH on 5-HT-induced antagonism of IAHP. In conclusion, our data indicated that the enhancement of 5-HT-induced excitation of DMV motoneurons by TRH described by in vivo rat experiments is not due to an interaction of TRH and 5-HT directly on the DMV motoneuron.

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