Is GABA release modulated by presynaptic receptors?

Nature ◽  
1978 ◽  
Vol 274 (5674) ◽  
pp. 904-905 ◽  
Author(s):  
P. R. MITCHELL ◽  
I. L. MARTIN
Keyword(s):  
Gaba Release ◽  
Presynaptic Receptors

scholarly journals 5-HT1B Receptor-Mediated Presynaptic Inhibition of GABA Release in the Suprachiasmatic Nucleus

2005 ◽  
Vol 93 (6) ◽  
pp. 3157-3164 ◽  
Author(s):  
Jayne R. Bramley ◽  
Patricia J. Sollars ◽  
Gary E. Pickard ◽  
F. Edward Dudek
Keyword(s):  
Suprachiasmatic Nucleus ◽  
Receptor Agonist ◽  
Gaba Release ◽  
Presynaptic Receptors ◽  
Clear Effect ◽  
Whole Cell Patch Clamp ◽  
Bath Application ◽  
Hypothalamic Slices ◽  
Photic Input ◽  
Serotonergic Innervation

The suprachiasmatic nucleus (SCN) receives a dense serotonergic innervation that modulates photic input to the SCN via serotonin 1B (5-HT1B) presynaptic receptors on retinal glutamatergic terminals. However, the majority of 5-HT1B binding sites in the SCN are located on nonretinal terminals and most axonal terminals in the SCN are GABAergic. We therefore tested the hypothesis that 5-HT1B receptors might also be located on SCN GABAergic terminals by examining the effects of the highly selective 5-HT1B receptor agonist CP-93,129 on SCN miniature inhibitory postsynaptic currents (mIPSCs). Whole cell patch-clamp recordings of mIPSCs were obtained from rat and mouse SCN neurons in hypothalamic slices. Using CsCl-containing microelectrodes with QX314, we isolated mPSCs that were sensitive to the GABAA receptor antagonist, bicuculline. Bath application of CP-93,129 (1 μM) decreased the frequency of mIPSCs by an average of 22% ( n = 7) in rat SCN neurons and by an average of 30% ( n = 8) in mouse SCN neurons with no clear effect on mIPSC amplitude. In mice lacking functional 5-HT1B receptors, CP-93,129 (1 μM) had no clear effect on the frequency or the amplitude of mIPSCs recorded in any of the cells tested ( n = 4). The decrease in the frequency of mIPSCs of SCN neurons produced by the selective 5-HT1B receptor agonist CP-93,129 is consistent with the interpretation that 5-HT1B receptors are located on GABA terminals in the SCN and that 5-HT inhibits GABA release via a 5-HT1B presynaptic receptor-mediated mechanism.

Effects of VPAC2 Receptor Activation on Membrane Excitability and GABAergic Transmission in Subparaventricular Zone Neurons Targeted by Suprachiasmatic Nucleus

2009 ◽  
Vol 102 (3) ◽  
pp. 1834-1842 ◽  
Author(s):  
M.L.H.J. Hermes ◽  
M. Kolaj ◽  
P. Doroshenko ◽  
E. Coderre ◽  
L. P. Renaud
Keyword(s):  
Suprachiasmatic Nucleus ◽  
Gaba Release ◽  
Receptor Activation ◽  
Presynaptic Receptors ◽  
Circadian Pacemaker ◽  
Membrane Excitability ◽  
Patch Clamp Recording ◽  
Subparaventricular Zone ◽  
Rat Brain Slice ◽  
Vip Receptor

The hypothalamic suprachiasmatic nucleus (SCN) harbors the master circadian pacemaker. SCN neurons produce the amino acid γ-aminobutyric acid (GABA) and several peptide molecules for coordination and communication of their circadian rhythms. A subpopulation of SCN cells synthesizes vasoactive intestinal polypeptide (VIP) and provides a dense innervation of the subparaventricular zone (SPZ), an important CNS target of the circadian pacemaker. In this study, using patch-clamp recording techniques and rat brain slice preparations, the contribution of VIP to SCN efferent signaling to SPZ was evaluated by examining membrane responses of SPZ neurons to exogenous VIP receptor ligands. In ∼50% of the SPZ neurons receiving monosynaptic GABAA receptor–mediated inputs from SCN, bath-applied VIP (0.5–1 μM) resulted in a membrane depolarization caused by tetrodotoxin-resistant inward currents reversing at ∼−23 mV. These data suggest the existence of postsynaptic receptors that activate a nonselective cationic conductance. In addition, a subset of SPZ neurons showed an increase in the amplitude of SCN-evoked GABAergic inhibitory postsynaptic currents (IPSCs) and a decrease in their paired-pulse ratios. This, together with an increase in frequency of spontaneous and miniature IPSCs, implies the presence of presynaptic receptors that facilitate GABA release from SCN and possibly other synaptic terminals. The effects occurred in separate neurons and could be mimicked by the selective VPAC2 receptor agonist BAY 55-9837 (0.2–0.5 μM) and partially blocked by the VIP receptor antagonist VIP(6-28) (5 μM). The results indicate that VIP acts via both post- and presynaptic VPAC2 receptors to differentially modulate SCN GABAergic signaling to distinct subpopulations of SPZ neurons.

Presynaptic inhibition of calcium-dependent and -independent release elicited with ionomycin, gadolinium, and alpha-latrotoxin in the hippocampus

1996 ◽  
Vol 75 (5) ◽  
pp. 2017-2028 ◽  
Author(s):  
M. Capogna ◽  
B. H. Gahwiler ◽  
S. M. Thompson
Keyword(s):  
Synaptic Transmission ◽  
Presynaptic Inhibition ◽  
Receptor Agonist ◽  
Gabab Receptor ◽  
Gaba Release ◽  
Presynaptic Receptors ◽  
Gamma Aminobutyric Acid ◽  
Calcium Dependent ◽  
Opioid Receptor Agonist ◽  
Voltage Dependent

1. Presynaptic inhibition of synaptic transmission in the hippocampus was investigated by comparing the effects of several agonists on miniature excitatory and inhibitory postsynaptic currents (mEPSCs and mIPSCs). 2. The Ca2+ ionophore ionomycin increased the frequency of mEPSCs and mIPSCs but did not affect their amplitude. Ionomycin-induced release required extracellular Ca2+ and was prevented by pretreatment with botulinum neurotoxin serotype F, like evoked synaptic transmission. Unlike evoked transmission, however, this increase did not involve activation of voltage-dependent Ca2+ channels because it was insensitive to Cd2+. 3. Both the lanthanide gadolinium and alpha-latrotoxin produced increases in the frequency of mEPSCs and mIPSCs, but their actions were independent of extracellular Ca2+. 4. Adenosine, the gamma-aminobutyric acid-B (GABAB) receptor agonist baclofen, and a mu-opioid receptor agonist strongly reduced the frequency of synaptic currents triggered by all three secretagogues. 5. We conclude that activation of these presynaptic receptors can reduce high frequencies of vesicular glutamate and GABA release by directly impairing transmitter exocytosis. Presynaptic inhibition of gadolinium- and alpha-latrotoxin-induced release indicates that this impairment occurs without changes in intraterminal Ca2+ homeostasis and when vesicle fusion is rendered Ca2+ independent, respectively. 6. The inhibition of ionomycin-induced release provides additional evidence for a direct, neurotransmitter receptor-mediated modulation of the proteins underlying vesicular docking or fusion as an important component of presynaptic inhibition of evoked synaptic transmission.

scholarly journals Desensitization-resistant and -sensitive GPCR-mediated inhibition of GABA release occurs by Ca2+-dependent and -independent mechanisms at a hypothalamic synapse

2016 ◽  
Vol 115 (5) ◽  
pp. 2376-2388 ◽  
Author(s):  
Reagan L. Pennock ◽  
Shane T. Hentges
Keyword(s):  
G Protein ◽  
Opioid Receptors ◽  
Transmitter Release ◽  
Presynaptic Inhibition ◽  
Calcium Influx ◽  
Gaba Release ◽  
Presynaptic Receptors ◽  
Postsynaptic Currents ◽  
Independent Mechanism ◽  
Μ Opioid Receptors

Whereas the activation of Gαi/o-coupled receptors commonly results in postsynaptic responses that show acute desensitization, the presynaptic inhibition of transmitter release caused by many Gαi/o-coupled receptors is maintained during agonist exposure. However, an exception has been noted where GABAB receptor (GABABR)-mediated inhibition of inhibitory postsynaptic currents (IPSCs) recorded in mouse proopiomelanocortin (POMC) neurons exhibit acute desensitization in ∼25% of experiments. To determine whether differential effector coupling confers sensitivity to desensitization, voltage-clamp recordings were made from POMC neurons to compare the mechanism by which μ-opioid receptors (MORs) and GABABRs inhibit transmitter release. Neither MOR- nor GABABR-mediated inhibition of release relied on the activation of presynaptic K+ channels. Both receptors maintained the ability to inhibit release in the absence of external Ca2+ or in the presence of ionomycin-induced Ca2+ influx, indicating that inhibition of release can occur through a Ca2+-independent mechanism. Replacing Ca2+ with Sr2+ to disrupt G-protein-mediated inhibition of release occurring directly at the release machinery did not alter MOR- or GABAB -mediated inhibition of IPSCs, suggesting that reductions in evoked release can occur through the inhibition of Ca2+ channels. Additionally, both receptors inhibited evoked IPSCs in the presence of selective blockers of N- or P/Q-type Ca2+ channels. Altogether, the results show that MORs and GABABRs can inhibit transmitter release through the inhibition of calcium influx and by direct actions at the release machinery. Furthermore, since both the desensitizing and nondesensitizing presynaptic receptors are similarly coupled, differential effector coupling is unlikely responsible for differential desensitization of the inhibition of release.

scholarly journals Kainate Acts at Presynaptic Receptors to Increase GABA Release From Hypothalamic Neurons

1999 ◽  
Vol 82 (2) ◽  
pp. 1059-1062 ◽  
Author(s):  
Qing-Song Liu ◽  
Peter R. Patrylo ◽  
Xiao-Bing Gao ◽  
Anthony N. van den Pol
Keyword(s):  
Transmitter Release ◽  
Hippocampal Neurons ◽  
Gaba Release ◽  
Presynaptic Receptors ◽  
Inhibitory Neurons ◽  
Kainate Receptors ◽  
Nmda Receptor Antagonists ◽  
Presynaptic Site ◽  
Site Of Action ◽  
Inhibitory Transmitter

Recent reports suggest that kainate acting at presynaptic receptors reduces the release of the inhibitory transmitter GABA from hippocampal neurons. In contrast, in the hypothalamus in the presence of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-d-aspartate (NMDA) receptor antagonists [1-(4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine (GYKI 52466) and d,l-2-amino-5-phosphonopentanoic acid (AP5)], kainate increased GABA release. In the presence of tetrodotoxin, the frequency, but not the amplitude, of GABA-mediated miniature inhibitory postsynaptic currents (IPSCs) was enhanced by kainate, consistent with a presynaptic site of action. Postsynaptic activation of kainate receptors on cell bodies/dendrites was also found. In contrast to the hippocampus where kainate increases excitability by reducing GABA release, in the hypothalamus where a much higher number of GABAergic cells exist, kainate-mediated activation of transmitter release from inhibitory neurons may reduce the level of neuronal activity in the postsynaptic cell.

Targeting angiotensin type-2 receptors located on pressor neurons in the nucleus of the solitary tract to relieve hypertension in mice

2021 ◽  
Author(s):  
Mazher Mohammed ◽  
Dominique N Johnson ◽  
Lei A Wang ◽  
Scott W Harden ◽  
Wanhui Sheng ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Gaba Release ◽  
Access Point ◽  
Central Administration ◽  
Solitary Tract ◽  
Arterial Blood ◽  
Pressor Responses ◽  
Pressure Lowering ◽  
Angiotensin Type

Abstract Aims These studies evaluate whether angiotensin type-2 receptors (AT2Rs) that are expressed on γ-aminobutyric acid (GABA) neurons in the nucleus of the solitary tract (NTS) represent a novel endogenous blood pressure-lowering mechanism. Methods and results Experiments combined advanced genetic and neuroanatomical techniques, pharmacology, electrophysiology, and optogenetics in mice to define the structure and cardiovascular-related function of NTS neurons that contain AT2R. Using mice with Cre-recombinase directed to the AT2R gene, we discovered that optogenetic stimulation of AT2R-expressing neurons in the NTS increases GABA release and blood pressure. To evaluate the role of the receptor, per se, in cardiovascular regulation, we chronically delivered C21, a selective AT2R agonist, into the brains of normotensive mice and found that central AT2R activation reduces GABA-related gene expression and blunts the pressor responses induced by optogenetic excitation of NTS AT2R neurons. Next, using in situ hybridization, we found that the levels of Agtr2 mRNAs in GABAergic NTS neurons rise during experimentally induced hypertension, and we hypothesized that this increased expression may be exploited to ameliorate the disease. Consistent with this, final experiments revealed that central administration of C21 attenuates hypertension, an effect that is abolished in mice lacking AT2R in GABAergic NTS neurons. Conclusion These studies unveil novel hindbrain circuits that maintain arterial blood pressure, and reveal a specific population of AT2R that can be engaged to alleviate hypertension. The implication is that these discrete receptors may serve as an access point for activating an endogenous depressor circuit.

scholarly journals Kisspeptin-8 Induces Anxiety-Like Behavior and Hypolocomotion by Activating the HPA Axis and Increasing GABA Release in the Nucleus Accumbens in Rats

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 112
Author(s):  
Katalin Eszter Ibos ◽  
Éva Bodnár ◽  
Zsolt Bagosi ◽  
Zsolt Bozsó ◽  
Gábor Tóth ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Ex Vivo ◽  
Gaba Release ◽  
Receptor Activation ◽  
Ambulatory Activity ◽  
Corticosterone Concentration ◽  
Reproductive Axis ◽  
Neuropeptide Ff ◽  
Serum Lh ◽  
Anxiogenic Effect

Kisspeptins (Kp) are RF-amide neuropeptide regulators of the reproductive axis that also influence anxiety, locomotion, and metabolism. We aimed to investigate the effects of intracerebroventricular Kp-8 (an N-terminally truncated octapeptide) treatment in Wistar rats. Elevated plus maze (EPM), computerized open field (OF), and marble burying (MB) tests were performed for the assessment of behavior. Serum LH and corticosterone levels were determined to assess kisspeptin1 receptor (Kiss1r) activation and hypothalamic-pituitary-adrenal axis (HPA) stimulation, respectively. GABA release from the nucleus accumbens (NAc) and dopamine release from the ventral tegmental area (VTA) and NAc were measured via ex vivo superfusion. Kp-8 decreased open arm time and entries in EPM, and also raised corticosterone concentration, pointing to an anxiogenic effect. Moreover, the decrease in arm entries in EPM, the delayed increase in immobility accompanied by reduced ambulatory activity in OF, and the reduction in interactions with marbles show that Kp-8 suppressed exploratory and spontaneous locomotion. The increase in GABA release from the NAc might be in the background of hypolocomotion by inhibiting the VTA-NAc dopaminergic circuitry. As Kp-8 raised LH concentration, it could activate Kiss1r and stimulate the reproductive axis. As Kiss1r is associated with hyperlocomotion, it is more likely that neuropeptide FF receptor activation is involved in the suppression of locomotor activity.

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