Robust GABAergic Regulation of the GnRH Neuron Distal Dendron
Xinhuai Liu1, Robert Porteous1, Allan E Herbison1,2
1Centre for Neuroendocrinology and Department of Physiology, University of Otago School of Biomedical Sciences, Dunedin 9054, New Zealand.
Endocrinology
|December 2, 2022
Summary
GABA regulates fertility by modulating GnRH neuron activity. GABAB receptor inhibition is dominant in male and female rodents, impacting GnRH secretion independently of kisspeptin signaling.
Area of Science:
- Neuroendocrinology
- Reproductive Biology
- Neurotransmitter Signaling
Background:
- Gonadotropin-releasing hormone (GnRH) neurons control fertility, and their activity is regulated by neurotransmitters.
- GnRH neurons possess a unique distal dendron involved in action potential propagation and kisspeptin-driven GnRH secretion.
Purpose of the Study:
- To investigate the role of gamma-aminobutyric acid (GABA) in regulating intracellular calcium concentrations ([Ca2+]) within the GnRH neuron distal dendron.
- To determine the specific GABA receptor subtypes involved and their influence on GnRH neuron activity in a sex- and cycle-dependent manner.
Main Methods:
- Utilized Gnrh1-Cre mice expressing the calcium sensor GCaMP6.
- Employed confocal imaging in acute brain slices to monitor [Ca2+] changes in the distal dendron.
- Applied GABA, muscimol, and baclofen to the dendron to assess receptor-specific effects.
Main Results:
- GABA application to the distal dendron caused either sustained [Ca2+] suppression or a biphasic response (elevation followed by suppression).
- GABAB receptor-mediated inhibition was prevalent in both sexes (80-100% in females, ~70% in males) and across the female estrous cycle.
- GABAA receptor-mediated excitation was infrequent in males and varied cyclically in females, peaking at proestrus.
- GABAB receptor activation significantly reduced the stimulatory effect of kisspeptin on the dendron.
Conclusions:
- The majority of GnRH neuron distal dendrons are subject to GABAergic regulation, primarily through GABAB receptors.
- This GABAergic control is sex- and estrous cycle-dependent, offering a novel pathway for regulating GnRH secretion.
- This mechanism provides a kisspeptin-independent pathway influencing both pulsatile and surge modes of GnRH release.
More Related Videos
07:16Methods for the Discovery of Novel Compounds Modulating a Gamma-Aminobutyric Acid Receptor Type A Neurotransmission
Published on: August 16, 2018
13.7K
09:30Dual Somatic Recordings from Gonadotropin-Releasing Hormone GnRH Neurons Identified by Green Fluorescent Protein GFP in Hypothalamic Slices
Published on: February 23, 2010
22.3K
Related Concept Videos
01:30Ligand-Gated Ion Channel Receptor: Gating Mechanism
2.4K
Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...
2.4K
01:22Activation and Inactivation of G Proteins
7.4K
Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high...
7.4K
01:21G-Protein Gated Ion Channels
4.7K
GPCRs are primarily responsible for our sense of smell, taste, and vision. The binding of a sensory stimulus activates GPCR to stimulate effector proteins, many of which are ion channels in the sensory organs. GPCRs modulate the opening and closing of the target ion channels either directly by binding them, or by releasing second messengers that activate these channels. As ions move across the membrane, the membrane potential is altered, which induces an appropriate response.
Sensory...
Sensory...
4.7K
01:12GPCR Desensitization
6.2K
G protein-coupled receptor (GPCR) signaling plays a crucial role in cell functioning. GPCR desensitization is an equally essential process. It allows cells to respond to changing environments and regain sensitivity to new stimuli while preventing unnecessary stimulation when no longer needed. Prolonged exposure to stimuli leads to GPCR desensitization. It involves blocking the receptors from binding and activating additional G proteins. This inhibits activation of downstream effectors, thereby...
6.2K
01:09GPCRs Regulate Adenylyl Cylase Activity
5.8K
Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
5.8K
01:27Adrenergic Neurons: Neurotransmission
4.0K
Postganglionic sympathetic fibers (except those supplying the sweat glands) releasing noradrenaline or norepinephrine are called noradrenergic or adrenergic neurons. Noradrenaline, dopamine, adrenaline, or epinephrine are collectively called "catecholamines" as they contain a catechol moiety and an amine side chain. The five stages of neurotransmitter release involve their synthesis, storage, release, reuptake and metabolism.
Synthesis: Catecholamine synthesis requires tyrosine, which...
Synthesis: Catecholamine synthesis requires tyrosine, which...
4.0K