Synchronized neuronal networks: The GnRH system

Witkin, Joan W.

doi:10.1002/(sici)1097-0029(19990101)44:1<11::aid-jemt3>3.0.co;2-w

Cited by 32 publications

(4 citation statements)

References 65 publications

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“…The distribution of EGFP ϩ ͞GnRH1 and GnRH subtypeimmunopositive fibers throughout the septal-preoptic hypothalamus, beneath the ependymal walls of the third ventricle, and surrounding the Aq of the midbrain is consistent with the proposed role of GnRH as a neuromodulator (18). Axosomatic and axodendritic synapses between GnRH1 elements have been reported in the rat and rhesus monkey (1,47). We now show GnRH fiber contacts between EGFP ϩ and EGFP Ϫ neurons, which may assist in the coordination of neuroendocrine and neuromodulatory actions of GnRH1.…”

Section: Septal-preoptic Hypothalamus Egfp ؉ ͞Gnrhsupporting

confidence: 76%

Nonmammalian gonadotropin-releasing hormone molecules in the brain of promoter transgenic rats

Parhar

Soga²,

Ogawa³

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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Mammalian gonadotropin-releasing hormone (GnRH1) and nonmammalian immunoreactive GnRH subtypes were examined in transgenic rats carrying an enhanced GFP (EGFP) reporter gene driven by a rat GnRH1 promoter. Double-label immunocytochemistry was performed on EGFP ؉ ͞GnRH1 brain sections by using antisera against GnRH1, GnRH2 (chicken II), GnRH3 (salmon), or seabream GnRH. EGFP ؉ ͞GnRH1 neurons were in the septalpreoptic hypothalamus but not in the midbrain, consistent with GnRH1-immunopositive neurons in WT rats. Apparent coexpression of EGFP ؉ ͞GnRH1 with other GnRH subtypes was observed. All EGFP ؉ neurons in the septal-preoptic hypothalamus were GnRH1-immunopositive. However, only Ϸ80% of GnRH1-immunopositive neurons were EGFP ؉ , which awaits further elucidation. GnRH subtypes-immunopositive fibers and EGFP ؉ ͞GnRH1 fibers were conspicuous in the organum vasculosum of the lamina terminalis, median eminence, and surrounding the ependymal walls of the third ventricle and the aqueduct in the midbrain. These results demonstrate that the expression of the EGFP-GnRH1 transgene is restricted to the bona fide GnRH1 population and provide clear morphological evidence supporting the existence of GnRH1 neuronal subpopulations in the septal-preoptic hypothalamus, which might be driven by different segments of the GnRH promoter. This genetic construct permits analyses of promoter usage in GnRH neurons, and our histochemical approaches open questions about functional relations among isoforms of this peptide, which regulates reproductive physiology in its behavioral and endocrine aspects.luteinizing hormone-releasing hormone ͉ double-label immunocytochemistry ͉ green fluorescent protein ͉ hypothalamus ͉ preoptic area

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Section: Septal-preoptic Hypothalamus Egfp ؉ ͞Gnrhsupporting

confidence: 76%

Nonmammalian gonadotropin-releasing hormone molecules in the brain of promoter transgenic rats

Parhar

Soga²,

Ogawa³

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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“…Neurotransmission by GnRH was first observed in bullfrog sympathetic ganglia (29) and subsequently in rat hippocampal neurons (30) and is believed to mediate neuroendocrine and sexual behavioral responses in the mammalian brain. Cultured GT1-7 cells, similar to normal GnRH neurons, exhibit sparse synaptic connections between individual cells that could serve to coordinate the activity of the neuronal network (31). These cells form very few gap junctions under the culture conditions of the present study and are predominantly possible by fibers that terminate on the perikarya and axons of adjacent neurons.…”

Section: Discussionmentioning

confidence: 75%

An agonist-induced switch in G protein coupling of the gonadotropin-releasing hormone receptor regulates pulsatile neuropeptide secretion

Krsmanović

Navarro

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

127

103

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The pulsatile secretion of gonadotropin-releasing hormone (GnRH) from normal and immortalized hypothalamic GnRH neurons is highly calcium-dependent and is stimulated by cAMP. It is also influenced by agonist activation of the endogenous GnRH receptor (GnRH-R), which couples to Gq/11 as indicated by release of membrane-bound ␣q/11 subunits and increased inositol phosphate͞Ca 2؉ signaling. Conversely, GnRH antagonists increase membrane-associated ␣q/11 subunits and abolish pulsatile GnRH secretion. GnRH also stimulates cAMP production but at high concentrations has a pertussis toxinsensitive inhibitory effect, indicative of receptor coupling to Gi. Coupling of the agonist-activated GnRH-R to both Gs and Gi proteins was demonstrated by the ability of nanomolar GnRH concentrations to reduce membrane-associated ␣s and ␣i3 levels and of higher concentrations to diminish ␣i3 levels. Conversely, ␣i3 was increased during GnRH antagonist and pertussis toxin treatment, with concomitant loss of pulsatile GnRH secretion. In cholera toxin-treated GnRH neurons, decreases in ␣s immunoreactivity and increases in cAMP production paralleled the responses to nanomolar GnRH concentrations. Treatment with cholera toxin and 8-bromo-cAMP amplified episodic GnRH pulses but did not affect their frequency. These findings suggest that an agonist concentration-dependent switch in coupling of the GnRH-R between specific G proteins modulates neuronal Ca 2؉ signaling via Gs-cAMP stimulatory and Gi-cAMP inhibitory mechanisms. Activation of Gi may also inhibit GnRH neuronal function and episodic secretion by regulating membrane ion currents. This autocrine mechanism could serve as a timer to determine the frequency of pulsatile GnRH release by regulating Ca 2؉ -and cAMPdependent signaling and GnRH neuronal firing.

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“…Furthermore, such electrical coupling via the dendritic processes could contribute to the coordination of the GnRH neurons of the hypothalamic preoptic area, which are more or less scattered and do not make cell cluster in the mammalian brains. In fact, morphological evidence in favor of this possibility has been reported in the mammalian hypothalamic GnRH neurons, but the functional significance of this remains to be studied (21,22).…”

Section: Coordinated Activity Of Gnrh Neurons and The Role Of Gap Junmentioning

confidence: 99%

Coordinated Synchronization in the Electrically Coupled Network of Terminal Nerve Gonadotropin-Releasing Hormone Neurons as Demonstrated by Double Patch-Clamp Study

Haneda

Oka

2008

Endocrinology

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The peptidergic neurons play important roles such as neuromodulatory and neuroendocrine functions in the central nervous system. However, our knowledge about the organization and the function of the peptidergic neuromodulator systems is still very poor. The terminal nerve GnRH peptidergic neurons of a teleost, the dwarf gourami (Colisa lalia), serve as an excellent model system for such study. The cell bodies are large and make up a tight cell cluster, and the easy access to the cell bodies on the ventral surface of the brain makes the electrophysiological measurements in a precisely controlled manner. Here we show direct evidence to demonstrate the electrical coupling and the synchronization of the neural firing activity among the terminal nerve GnRH neurons by using the double patch-clamp recording technique. The electrical coupling coefficient was strong enough (ranged from 0.083 to 0.370) to synchronize spontaneous firings of GnRH neurons in the cluster. A model, in which the firings in the cluster occur within a small time window (dozens of milliseconds), was verified by using the serial loose-seal extracellular patch-clamp recordings and the cross-correlogram analysis. The present findings provide several insights for understanding the physiological mechanisms and functional significance of synchronized activities in the peptidergic and/or aminergic neuromodulator system as well as in the peptidergic neuroendocrine cells.

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Synchronized neuronal networks: The GnRH system

Cited by 32 publications

References 65 publications

Nonmammalian gonadotropin-releasing hormone molecules in the brain of promoter transgenic rats

Nonmammalian gonadotropin-releasing hormone molecules in the brain of promoter transgenic rats

An agonist-induced switch in G protein coupling of the gonadotropin-releasing hormone receptor regulates pulsatile neuropeptide secretion

Coordinated Synchronization in the Electrically Coupled Network of Terminal Nerve Gonadotropin-Releasing Hormone Neurons as Demonstrated by Double Patch-Clamp Study

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