Dopamine D4 Receptor-Mediated Presynaptic Inhibition of GABAergic Transmission in the Rat Supraoptic Nucleus

2003 ◽  
Vol 90 (2) ◽  
pp. 559-565 ◽  
Author(s):  
Karima Azdad ◽  
Richard Piet ◽  
Dominique A. Poulain ◽  
Stéphane H. R. Oliet
Keyword(s):  
Supraoptic Nucleus ◽  
Sch 23390 ◽  
Hormone Release ◽  
D3 Receptor ◽  
Receptor Antagonists ◽  
Gabaergic Transmission ◽  
Inhibitory Postsynaptic Currents ◽  
Postsynaptic Currents ◽  
D4 Receptor ◽  
Supraoptic Neurons

The mechanism by which dopamine induces or facilitates neurohypophysial hormone release is not completely understood. Because oxytocin- and vasopressin-secreting supraoptic neurons are under the control of a prominent GABAergic inhibition, we investigated the possibility that dopamine exerts its action by modulating GABA-mediated transmission. Whole cell voltage-clamp recordings of supraoptic neurons were carried out in acute hypothalamic slices to determine the action of dopamine on inhibitory postsynaptic currents. Application of dopamine caused a consistent and reversible reduction in the frequency, but not the amplitude, of miniature synaptic events, indicating that dopamine was acting presynaptically to reduce GABAergic transmission. The subtype of dopamine receptor involved in this response was characterized pharmacologically. Dopamine inhibitory action was greatly reduced by two highly selective D4 receptor antagonists L745,870 and L750,667 and to a lower extent by the antipsychotic drug clozapine but was unaffected by SCH 23390 and sulpiride, D1/D5 and D2/D3 receptor antagonists, respectively. In agreement with these results, the action of dopamine was mimicked by the potent D4 receptor agonist PD168077 but not by SKF81297 and bromocriptine, D1/D5 and D2/D3 receptor agonists, respectively. Dopamine and PD168077 also reduced the amplitude of evoked inhibitory postsynaptic currents, an effect that was accompanied by an increase in paired-pulse facilitation. These data clearly indicate that D4 receptors are located on GABA terminals in the supraoptic nucleus and that their activation reduces GABA release in the supraoptic nucleus. Therefore dopaminergic facilitation of neurohypophysial hormone release appears to result, at least in part, from disinhibition of magnocellular neurons caused by the depression of GABAergic transmission.

Dopamine D4 Receptor Activation Inhibits Presynaptically Glutamatergic Neurotransmission in the Rat Supraoptic Nucleus

2001 ◽  
Vol 86 (3) ◽  
pp. 1149-1155 ◽  
Author(s):  
Christopher J. Price ◽  
Quentin J. Pittman
Keyword(s):  
Supraoptic Nucleus ◽  
Sch 23390 ◽  
Receptor Activation ◽  
Glutamatergic Neurotransmission ◽  
Magnocellular Neurons ◽  
Vasopressin Release ◽  
Paired Pulse ◽  
Postsynaptic Currents ◽  
Whole Cell Patch Clamp ◽  
D4 Receptor

Oxytocin and vasopressin release from magnocellular neurons of the supraoptic nucleus is under the control of glutamate-dependent excitation. The supraoptic nucleus also receives a generalized dopaminergic input from hypothalamic sources. To determine if dopamine can influence this excitatory drive onto the magnocellular neurons, we used whole-cell patch clamp to record the effect of dopamine on evoked and miniature excitatory postsynaptic currents in rat hypothalamic slices. Dopamine exposure (30 μM to 1 mM) induced a large and reversible reduction in the amplitude of evoked excitatory postsynaptic current in nearly all magnocellular cells tested. D4 receptors appeared to mediate dopamine's activity, based on inhibition of the response with 50 μM clozapine, but not by SCH 23390 or sulpiride, and mimicry of dopamine's action with the D4 specific agonist, PD 168077. Analysis of paired-pulse experiments and miniature postsynaptic currents indicated that dopamine's action involved a presynaptic mechanism, since the frequency of miniature postsynaptic currents was reduced with dopamine exposure without any change in current kinetics or amplitude, while the paired-pulse ratio increased. We therefore have demonstrated for the first time a role for dopamine D4 receptors in the supraoptic nucleus in the presynaptic inhibition of glutamatergic neurotransmission onto magnocellular neurons.

Brain-derived neurotrophic factor inhibits spontaneous inhibitory postsynaptic currents in the rat supraoptic nucleus

2009 ◽  
Vol 1258 ◽  
pp. 34-42 ◽  
Author(s):  
Toyoaki Ohbuchi ◽  
Toru Yokoyama ◽  
Takeshi Saito ◽  
Hirofumi Hashimoto ◽  
Hitoshi Suzuki ◽  
...  
Keyword(s):  
Neurotrophic Factor ◽  
Supraoptic Nucleus ◽  
Brain Derived Neurotrophic Factor ◽  
Inhibitory Postsynaptic Currents ◽  
Postsynaptic Currents

Increased GABAergic transmission in neuropeptide Y-expressing neurons in the dopamine-depleted murine striatum

2020 ◽  
Vol 123 (4) ◽  
pp. 1496-1503
Author(s):  
Lena Rubi ◽  
Jean-Marc Fritschy
Keyword(s):  
Neuropeptide Y ◽  
Skill Learning ◽  
Projection Neurons ◽  
Dopamine Depletion ◽  
Functional Impairments ◽  
Patch Clamp Technique ◽  
Gabaergic Transmission ◽  
Inhibitory Postsynaptic Currents ◽  
Cholinergic Interneurons ◽  
Postsynaptic Currents

As the main input nucleus of the basal ganglia, the striatum plays a central role in planning, control, and execution of movement and motor skill learning. More than 90% of striatal neurons, so-called medium spiny neurons (MSN), are GABAergic projection neurons, innervating primarily the substantia nigra pars reticulata or the globus pallidus internus. The remaining neurons are GABAergic and cholinergic interneurons, synchronizing and controlling striatal output by reciprocal connections with MSN. Besides prominent local cholinergic influence, striatal function is globally regulated by dopamine (DA) from the nigrostriatal pathway. Little is known about whether DA depletion, as occurs in Parkinson’s disease, affects the activity of striatal interneurons. Here we focused on neuropeptide Y (NPY)-expressing interneurons, which are among the major subgroups of GABAergic interneurons in the striatum. We investigated the effects of striatal DA depletion on GABAergic transmission in NPY interneurons by electrophysiologically recording GABAergic spontaneous (s) and miniature (m) inhibitory postsynaptic currents (IPSCs) in identified NPY interneurons in slices from 6-hydroxydopamine (6-OHDA)- and vehicle-injected transgenic NPY-humanized Renilla green fluorescent protein (hrGFP) mice with the whole cell patch-clamp technique. We report a significant increase in sIPSC and mIPSC frequency as well as the occurrence of giant synaptic and burst sIPSCs in the 6-OHDA group, suggesting changes in GABAergic circuit activity and synaptic transmission. IPSC kinetics remained unchanged, pointing to mainly presynaptic changes in GABAergic transmission. These results show that chronic DA depletion following 6-OHDA injection causes activity-dependent and -independent increase of synaptic GABAergic inhibition onto striatal NPY interneurons, confirming their involvement in the functional impairments of the DA-depleted striatum. NEW & NOTEWORTHY Neuropeptide Y (NPY) interneurons regulate the function of striatal projection neurons and are upregulated upon dopamine depletion in the striatum. Here we investigated how dopamine depletion affects NPY circuits and show electrophysiologically that it leads to the occurrence of giant synaptic and burst GABAergic spontaneous inhibitory postsynaptic currents (IPSCs) and to an activity-independent increase in GABAergic miniature IPSC frequency in NPY neurons. We suggest that degeneration of dopaminergic terminals in the striatum causes functional changes in striatal GABAergic function.

Histamine Suppresses Non-NMDA Excitatory Synaptic Currents in Rat Supraoptic Nucleus Neurons

2000 ◽  
Vol 83 (5) ◽  
pp. 2616-2625 ◽  
Author(s):  
Zhenhui Li ◽  
Glenn I. Hatton
Keyword(s):  
Supraoptic Nucleus ◽  
Synaptic Currents ◽  
Excitatory Postsynaptic Currents ◽  
Paired Pulse ◽  
Paired Pulse Facilitation ◽  
Postsynaptic Currents ◽  
Whole Cell Patch Clamp ◽  
Bath Application ◽  
Intracellular Diffusion ◽  
Supraoptic Neurons

Whole cell patch-clamp recordings were obtained from supraoptic neurons to investigate the effects of histamine on excitatory postsynaptic currents evoked by electrical stimulation of areas around the posterior supraoptic nucleus. When cells were voltage-clamped at −70 mV, evoked excitatory postsynaptic currents had amplitudes of 88.4 ± 9.6 pA and durations of 41.1 ± 3.0 ms (mean ± SE; n = 43). With twin stimulus pulses (20 Hz) used, paired-pulse facilitation ratios were 1.93 ± 0.12. Bath application of 6-cyano-7-nitroquinoxalene-2,3-dione (CNQX) abolished synaptic currents. Histamine at concentrations ∼0.1–10 μM reversibly suppressed excitatory postsynaptic currents in all supraoptic neurons tested. Within 2 min after application of (10 μM) histamine, current amplitudes and durations decreased by 61.5 and 31.0%, respectively, with little change in the paired-pulse facilitation ratio. Dimaprit or imetit (H2 or H3 receptor agonists) did not reduce synaptic currents, whereas pyrilamine (H1 receptor antagonist) blocked histamine-induced suppression of synaptic currents. When patch electrodes containing guanosine 5′- O-(2-thiodiphosphate) (GDP-β-S) were used to record cells, histamine still suppressed current amplitudes by 49.1% and durations by 41.9%. Similarly, intracellular diffusion of bis-( o-aminophenoxy)- N,N,N′,N′-tetraacetic acid (BAPTA) and H7 did not abolish histamine-induced suppression of synaptic currents, either. Bath perifusion of 8-bromo-quanosine 3′,5′-cyclic monophosphate reduced current amplitudes by 32.3% and durations by 27.9%. After bath perfusion of slices with Nω-nitro-l-arginine methyl ester (L-NAME), histamine injection decreased current amplitudes only by 31.9%, much less than the inhibition rate in control ( P < 0.01). In addition, histamine induced little change in current durations and paired-pulse facilitation ratios, representing a partial blockade of histamine effects on synaptic currents by L-NAME. In supraoptic neurons recorded using electrodes containing BAPTA and perifused with L-NAME, the effects of histamine on synaptic currents were completely abolished. Norepinephrine injection reversibly decreased current amplitudes by 39.1% and duration by 64.5%, with a drop in the paired-pulse facilitation ratio of 47.9%. Bath perifusion of L-NAME, as well as intracellular diffusion of GDP-β-S, , 1-(5-isoquinolinylsulfonyl)-2-methyl-piperazine , or BAPTA, failed to block norepinephrine-induced suppression of evoked synaptic currents. The present results suggest that histamine suppresses non- N-methyl-d-aspartate synaptic currents in supraoptic neurons through activation of H1receptors. It is possible that histamine first acts at supraoptic cells (perhaps both neuronal and nonneuronal) and induces the production of nitric oxide, which then diffuses to nearby neurons and modulates synaptic transmission by a postsynaptic mechanism.

Inhibition of spontaneous inhibitory postsynaptic currents (IPSC) by noradrenaline in rat supraoptic neurons through presynaptic α2-adrenoceptors

1998 ◽  
Vol 807 (1-2) ◽  
pp. 61-69 ◽  
Author(s):  
Yu-Feng Wang ◽  
Izumi Shibuya ◽  
Narutoshi Kabashima ◽  
V.Sutarmo Setiadji ◽  
Toyohi Isse ◽  
...  
Keyword(s):  
Α2 Adrenoceptors ◽  
Inhibitory Postsynaptic Currents ◽  
Postsynaptic Currents ◽  
Supraoptic Neurons

Actions of Midazolam on GABAergic Transmission in Substantia Gelatinosa Neurons of Adult Rat Spinal Cord Slices

2000 ◽  
Vol 92 (2) ◽  
pp. 507-507 ◽  
Author(s):  
Tatsuro Kohno ◽  
Eiichi Kumamoto ◽  
Hiroshi Baba ◽  
Toyofumi Ataka ◽  
Manabu Okamoto ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Benzodiazepine Receptor ◽  
Substantia Gelatinosa ◽  
Rat Spinal Cord ◽  
Gabaergic Transmission ◽  
Gaba A ◽  
Inhibitory Postsynaptic Currents ◽  
Adult Rat ◽  
Postsynaptic Currents ◽  
Adult Rat Spinal Cord

Background Although intrathecal administration of midazolam has been found to produce analgesia, how midazolam exerts this effect is not understood fully at the neuronal level in the spinal cord. Methods The effects of midazolam on either electrically evoked or spontaneous inhibitory transmission and on a response to exogenous gamma-aminobutyric acid (GABA), a GABA(A)-receptor agonist, muscimol, or glycine were evaluated in substantia gelatinosa neurons of adult rat spinal cord slices by using the whole-cell patch-clamp technique. Results Bath-applied midazolam (1 microM) prolonged the decay phase of evoked and miniature inhibitory postsynaptic currents (IPSCs), mediated by GABA(A) receptors, without a change in amplitudes, while not affecting glycine receptor-mediated miniature inhibitory postsynaptic currents in both the decay phase and the amplitude. Either GABA- or muscimol-induced currents were enhanced in amplitude by midazolam (0.1 microM) in a manner sensitive to a benzodiazepine receptor antagonist, flumazenil (1 microM); glycine currents were, however, unaltered by midazolam. Conclusions Midazolam augmented both the duration of GABA-mediated synaptic current and the amplitude of GABA-induced current by acting on the GABA(A)-benzodiazepine receptor in substantia gelatinosa neurons; this would increase the inhibitory GABAergic transmission. This may be a possible mechanism for antinociception by midazolam.

GABAA Receptor β3 Subunit Deletion Decreases α2/3 Subunits and IPSC Duration

2003 ◽  
Vol 89 (1) ◽  
pp. 128-134 ◽  
Author(s):  
Epolia Ramadan ◽  
Zhanyan Fu ◽  
Gabriele Losi ◽  
Gregg E. Homanics ◽  
Joseph H. Neale ◽  
...  
Keyword(s):  
Gabaa Receptor ◽  
Cortical Neurons ◽  
Behavioral Deficits ◽  
Inhibitory Postsynaptic Currents ◽  
Postsynaptic Currents ◽  
Surface Staining ◽  
Α1 Subunit

Deletion of the β3 subunit of the GABAA receptor produces severe behavioral deficits and epilepsy. GABAA receptor-mediated miniature inhibitory postsynaptic currents (mIPSCs) in cortical neurons in cultures from β3 −/− mice were significantly faster than those in β3 +/+ mice and were more prolonged by zolpidem. Surface staining revealed that the number of β2/3, α2, and α3 (but not of α1) subunit-expressing neurons and the intensity of subunit clusters were significantly reduced in β3 −/− mice. Transfection of β3 −/− neurons with β3 cDNA restored β2/3, α2, and α3 subunits immunostaining and slowed mIPSCs decay. We show that the deletion of the β3 subunit causes the loss of a subset of GABAA receptors with α2 and α3 subunits while leaving a receptor population containing predominantly α1 subunit with fast spontaneous IPSC decay and increased zolpidem sensitivity.

scholarly journals Isoflurane Differentially Modulates Inhibitory and Excitatory Synaptic Transmission to the Solitary Tract Nucleus

2008 ◽  
Vol 108 (4) ◽  
pp. 675-683 ◽  
Author(s):  
James H. Peters ◽  
Stuart J. McDougall ◽  
David Mendelowitz ◽  
Dennis R. Koop ◽  
Michael C. Andresen
Keyword(s):  
Nucleus Tractus Solitarius ◽  
Second Order ◽  
Visceral Afferents ◽  
Gas Chromatography Mass Spectrometry ◽  
Gamma Aminobutyric Acid ◽  
Solitary Tract ◽  
Excitatory Postsynaptic Currents ◽  
Inhibitory Postsynaptic Currents ◽  
Postsynaptic Currents ◽  
Presynaptic Mechanisms

Background Isoflurane anesthesia produces cardiovascular and respiratory depression, although the specific mechanisms are not fully understood. Cranial visceral afferents, which innervate the heart and lungs, synapse centrally onto neurons within the medial portion of the nucleus tractus solitarius (NTS). Isoflurane modulation of afferent to NTS synaptic communication may underlie compromised cardiorespiratory reflex function. Methods Adult rat hindbrain slice preparations containing the solitary tract (ST) and NTS were used. Shocks to ST afferents evoked excitatory postsynaptic currents with low-variability (SEM &lt;200 mus) latencies identifying neurons as second order. ST-evoked and miniature excitatory postsynaptic currents as well as miniature inhibitory postsynaptic currents were measured during isoflurane exposure. Perfusion bath samples were taken in each experiment to measure isoflurane concentrations by gas chromatography-mass spectrometry. Results Isoflurane dose-dependently increased the decay-time constant of miniature inhibitory postsynaptic currents. At greater than 300 mum isoflurane, the amplitude of miniature inhibitory postsynaptic currents was decreased, but the frequency of events remained unaffected, whereas at equivalent isoflurane concentrations, the frequency of miniature excitatory postsynaptic currents was decreased. ST-evoked excitatory postsynaptic current amplitudes decreased without altering event kinetics. Isoflurane at greater than 300 mum increased the latency to onset and rate of synaptic failures of ST-evoked excitatory postsynaptic currents. Conclusions In second-order NTS neurons, isoflurane enhances phasic inhibitory transmission via postsynaptic gamma-aminobutyric acid type A receptors while suppressing excitatory transmission through presynaptic mechanisms. These results suggest that isoflurane acts through multiple distinct mechanisms to inhibit neurotransmission within the NTS, which would underlie suppression of homeostatic reflexes.

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