Glutamate regulation of GnRH neuron excitability

Iremonger, Karl J.; Constantin, Stéphanie; Liu, Xinhuai; Herbison, Allan E.

doi:10.1016/j.brainres.2010.08.071

Cited by 97 publications

(82 citation statements)

References 61 publications

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“…This is reminiscent of the observation that only 19% of GnRH neurons have spontaneous postsynaptic currents mediated by both AMPA and NMDA receptors (Christian et al, 2009). The relative absence of NMDA receptor involvement is in agreement with other brain slice studies indicating that only 10 -30% of adult GnRH neurons express functional NMDA receptors (Spergel et al, 1999;Christian et al, 2009;Iremonger et al, 2010).…”

Section: Discussionsupporting

confidence: 91%

“…This result is surprising considering that glutamatergic neurons are plentiful in the AVPV (Ottem et al, 2004) and most GnRH neurons express functional glutamate receptors (Iremonger et al, 2010). Virtually all GnRH neurons exhibit spines (Campbell et al, 2005(Campbell et al, , 2009), indicative of glutamatergic inputs, and the majority exhibit electrophysiological evidence of functional glutamate receptors (Spergel et al, 1999;Christian et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

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

Liu¹,

Porteous²,

Tassigny³

et al. 2011

J. Neurosci.

112

128

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The anteroventral periventricular nucleus (AVPV) is thought to play a key role in regulating the excitability of gonadotropin-releasing hormone (GnRH) neurons that control fertility. Using an angled, parahorizontal brain slice preparation we have undertaken a series of electrophysiological experiments to examine how the AVPV controls GnRH neurons in adult male and female mice. More than half (59%) of GnRH neurons located in the rostral preoptic area were found to receive monosynaptic inputs from the AVPV in a sex-dependent manner. AVPV stimulation frequencies Ͻ1 Hz generated short-latency action potentials in GnRH neurons with GABA and glutamate mediating Ͼ90% of the evoked fast synaptic currents. The AVPV GABA input was dominant and found to excite or inhibit GnRH neurons in a cell-dependent manner. Increasing the AVPV stimulation frequency to 5-10 Hz resulted in the appearance of additional poststimulus inhibitory as well as delayed excitatory responses in GnRH neurons that were independent of ionotropic amino acid receptors. The inhibition observed immediately following the end of the stimulation period was mediated partly by GABA B receptors, while the delayed activation was mediated by the neuropeptide kisspeptin. The latter response was essentially absent in Gpr54 knock-out mice and abolished by a Gpr54 antagonist. Together, these studies show that AVPV neurons provide direct amino acid and neuropeptidergic inputs to GnRH neurons. Low-frequency activation generates predominant GABA/glutamate release with higher frequency activation recruiting release of kisspeptin. This frequency-dependent release of amino acid and neuropeptide neurotransmitters greatly expands the range of AVPV control of GnRH neuron excitability.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

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

Liu¹,

Porteous²,

Tassigny³

et al. 2011

J. Neurosci.

112

128

View full text Add to dashboard Cite

show abstract

“…As reviewed by Iremonger and coworkers (Iremonger et al 2010), many studies have shown that glutamate agonists and antagonists injected into the brain can stimulate or inhibit LH secretion, respectively (Lopez et al 1990, Brann & Mahesh 1995, Ping et al 1997. Glutamate likely exerts its influence via direct effects on GNRH neurons, as TenaSempere's lab demonstrated that glutamate-stimulated LH secretion occurs in a kisspeptin-independent manner (Garcia-Galiano et al 2012).…”

Section: Glutamate-expressing Neuronsmentioning

confidence: 99%

Neuroendocrine integration of nutritional signals on reproduction

Evans

Anderson

2017

Journal of Molecular Endocrinology

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Reproductive function in mammals is energetically costly and therefore tightly regulated by nutritional status. To enable this integration of metabolic and reproductive function, information regarding peripheral nutritional status must be relayed centrally to the gonadotropin-releasing hormone (GNRH) neurons that drive reproductive function. The metabolically relevant hormones leptin, insulin and ghrelin have been identified as key mediators of this 'metabolic control of fertility'. However, the neural circuitry through which they act to exert their control over GNRH drive remains incompletely understood. With the advent of Cre-LoxP technology, it has become possible to perform targeted gene-deletion and gene-rescue experiments and thus test the functional requirement and sufficiency, respectively, of discrete hormone-neuron signaling pathways in the metabolic control of reproductive function. This review discusses the findings from these investigations, and attempts to put them in context with what is known from clinical situations and wild-type animal models. What emerges from this discussion is clear evidence that the integration of nutritional signals on reproduction is complex and highly redundant, and therefore, surprisingly difficult to perturb. Consequently, the deletion of individual hormone-neuron signaling pathways often fails to cause reproductive phenotypes, despite strong evidence that the targeted pathway plays a role under normal physiological conditions. Although transgenic studies rarely reveal a critical role for discrete signaling pathways, they nevertheless prove to be a good strategy for identifying whether a targeted pathway is absolutely required, critically involved, sufficient or dispensable in the metabolic control of fertility.

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“…It is widely accepted that glutamate plays important roles in controlling GnRH neuron excitability, probably acting at the preoptic region of the hypothalamus (Gu et al, 1999). Only small sub-populations of GnRH neurons have functional mGluRs (Iremonger et al, 2010). A subpopulation of GnRH neurons in the medial septum was found to be excited by group I mGluR agonists (Dumalska et al, 2008).…”

Section: Effects Of Mglur Activation On Hypothalamic Neuropeptide Relmentioning

confidence: 99%

Metabotropic Glutamate Receptors in Peripheral Tissues: Implications for Toxicology

Durand¹,

Carniglia²,

Caruso³

et al. 2011

Anxiety Disorders

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Glutamate regulation of GnRH neuron excitability

Cited by 97 publications

References 61 publications

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

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

Neuroendocrine integration of nutritional signals on reproduction

Metabotropic Glutamate Receptors in Peripheral Tissues: Implications for Toxicology

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