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.

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.

scholarly journals Influences of Morphine on the Spontaneous and Evoked Excitatory Postsynaptic Currents in Lateral Amygdala of Rats

2016 ◽  
pp. 165-169 ◽  
Author(s):  
J.-J. ZHANG ◽  
X.-D. LIU ◽  
L.-C. YU
Keyword(s):  
Synaptic Transmission ◽  
Excitatory Synaptic Transmission ◽  
Morphine Treatment ◽  
Lateral Amygdala ◽  
Excitatory Postsynaptic Currents ◽  
Postsynaptic Currents ◽  
Whole Cell Patch Clamp ◽  
The Central Nervous System ◽  
Underlying Mechanisms

Acute morphine exposure induces antinociceptive activity, but the underlying mechanisms in the central nervous system are unclear. Using whole-cell patch clamp recordings, we explore the role of morphine in the modulation of excitatory synaptic transmission in lateral amygdala neurons of rats. The results demonstrate that perfusion of 10 μM of morphine to the lateral amygdala inhibits the discharge frequency significantly. We further find that there are no significant influences of morphine on the amplitude of spontaneous excitatory postsynaptic currents (sEPSCs). Interestingly, morphine shows no marked influence on the evoked excitatory postsynaptic currents (eEPSCs) in the lateral amygdala neurons. These results indicate that acute morphine treatment plays an important role in the modulation on the excitatory synaptic transmission in lateral amygdala neurons of rats.

Activation of adenosine A2A receptors alters postsynaptic currents and depolarizes neurons of the supraoptic nucleus

2006 ◽  
Vol 291 (2) ◽  
pp. R359-R366 ◽  
Author(s):  
Todd A. Ponzio ◽  
Yu-Feng Wang ◽  
Glenn I. Hatton
Keyword(s):  
Supraoptic Nucleus ◽  
Cell Activity ◽  
Brain Slices ◽  
Cell Types ◽  
Receptor Activation ◽  
A2a Receptors ◽  
Postsynaptic Currents ◽  
Cgs 21680 ◽  
Whole Cell Patch Clamp ◽  
Sites Of Action

Supraoptic nucleus (SON) neurons secrete oxytocin or vasopressin in response to various physiological stimuli (e.g., lactation/suckling, dehydration). Released near fenestrated capillaries of the neurohypophysis, these peptides enter the blood and travel to peripheral target organs. The pervasive neuromodulator adenosine, acting at A1 receptors, is an important inhibitory regulator of magnocellular neuroendocrine cell activity. Another high-affinity adenosine receptor exists in this system, however. We examined the physiological effects of adenosine A2A receptor activation and determined its localization among various cell types within the SON. In whole cell patch-clamp recordings from rat brain slices, application of the selective adenosine A2A receptor agonist CGS-21680 caused membrane depolarizations in SON neurons, often leading to increased firing activity. Membrane potential changes were persistent (>10 min) and could be blocked by the selective A2A receptor antagonist ZM-241385, or GDP-β-S, the latter suggesting postsynaptic sites of action. However, ±-α-methyl-(4-carboxyphenyl)glycine or TTX also blocked CGS-21680 effects, indicating secondary actions on postsynaptic neurons. In voltage-clamp mode, application of CGS-21680 caused a slight increase (∼8%) in high-frequency clusters of excitatory postsynaptic currents. With the use of specific antibodies, adenosine A2A receptors were immunocytochemically localized to both the magnocellular neurons and astrocytes of the SON. Ecto-5′nucleotidase, an enzyme involved in the metabolism of ATP to adenosine, was also localized to astrocytes of the SON. These results demonstrate that adenosine acting at A2A receptors can enhance the excitability of SON neurons and modulate transmitter release from glutamatergic afferents projecting to the nucleus. We suggest that adenosine A2A receptors may function in neuroendocrine regulation through both direct neuronal mechanisms and via actions involving glia.

scholarly journals Cortical potentiation induced by calcitonin gene-related peptide (CGRP) in the insular cortex of adult mice

2020 ◽  
Author(s):  
Yinlu Liu ◽  
Qi-Yu Chen ◽  
Jung Hyun Lee ◽  
Xu-Hui Li ◽  
Shengyuan Yu ◽  
...  
Keyword(s):  
Insular Cortex ◽  
Calcitonin Gene Related Peptide ◽  
Anterior Cingulate ◽  
Excitatory Postsynaptic Currents ◽  
Postsynaptic Currents ◽  
Related Peptide ◽  
Excitatory Transmission ◽  
Bath Application ◽  
Calcitonin Gene ◽  
Presynaptic Mechanisms

Abstract Recent studies demonstrate that calcitonin gene-related peptide (CGRP) plays critical roles in migraine. Immunohistochemistry and in situ hybridization studies have shown that CGRP and its receptors are expressed in cortical areas that are critical for pain perception including the anterior cingulate cortex (ACC) and insular cortex (IC). Recent studies reported that CGRP enhanced excitatory transmission in the ACC. However, little is known about the possible effect of CGRP on excitatory transmission in the IC. In the present study, we investigated the role of CGRP on synaptic transmission in the IC slices of adult male mice. Bath application of CGRP produced dose-dependent potentiation of evoked excitatory postsynaptic currents (eEPSCs). This potentiation was NMDA receptor (NMDAR) independent. After application of CGRP1 receptor antagonist CGRP8-37 or BIBN 4096, CGRP produced potentiation was significantly reduced. Paired-pulse facilitation was significantly decreased by CGRP, suggesting possible presynaptic mechanisms. Consistently, bath application of CGRP significantly increased the frequency of spontaneous and miniature excitatory postsynaptic currents (sEPSCs and mEPSCs). By contrast, amplitudes of sEPSCs and mEPSCs were not significantly affected. Finally, adenylyl cyclase subtype 1 (AC1) and protein kinase A (PKA) are critical for CGRP-produced potentiation, since both selective AC1 inhibitor NB001 and the PKA inhibitor KT5720 completely blocked the potentiation. Our results provide direct evidence that CGRP contributes to synaptic potentiation in the IC, and the AC1 inhibitor NB001 may be beneficial for the treatment of migraine in the future.

scholarly journals Presynaptic glutamatergic transmission and feedback system of oxytocinergic neurons in the hypothalamus of a rat model of adjuvant arthritis

2020 ◽  
Vol 16 ◽  
pp. 174480692094333
Author(s):  
Teruaki Fujitani ◽  
Takanori Matsuura ◽  
Makoto Kawasaki ◽  
Hitoshi Suzuki ◽  
Haruki Nishimura ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Paraventricular Nucleus ◽  
Rat Model ◽  
Adjuvant Arthritis ◽  
Fluorescent Protein ◽  
Feedback System ◽  
Red Fluorescent Protein ◽  
Excitatory Postsynaptic Currents ◽  
Postsynaptic Currents ◽  
Bath Application

The neurohypophysial hormone oxytocin (OXT) is synthesized in the hypothalamic paraventricular and supraoptic nuclei. Recently, some studies have considered OXT to be important in sensory modulation and that the OXT protein is upregulated by acute and chronic nociception. However, the mechanism by which OXT is upregulated in neurons is unknown. In this study, we examined the resting membrane potentials and excitatory postsynaptic currents in OXT-ergic neurons in the paraventricular nucleus in adjuvant arthritis rat model, a model of chronic inflammation, using whole-cell patch-clamping. Transgenic rats expressing OXT and monomeric red fluorescent protein 1 (mRFP1) fusion protein to visualize the OXT-ergic neurons were used, and the OXT-mRFP1 transgenic rat model of adjuvant arthritis was developed by injection of heat-killed Mycobacterium butyricum. Furthermore, the feedback system of synthesized OXT was also examined using the OXT receptor antagonist L-368,899. We found that the resting membrane potentials and frequency of miniature excitatory postsynaptic currents and spontaneous excitatory postsynaptic currents in OXT-monomeric red fluorescent protein 1 neurons in the paraventricular nucleus were significantly increased in adjuvant arthritis rats. Furthermore, L-368,899 dose-dependently increased the frequency of miniature excitatory postsynaptic currents and spontaneous excitatory postsynaptic currents in OXT-ergic neurons. Following bath application of the GABAA receptor antagonist picrotoxin and the cannabinoid receptor 1 antagonist AM 251, L-368,899 still increased the frequency of miniature excitatory postsynaptic currents. However, following bath application of the nitric oxide synthase inhibitor Nω-Nitro-L-arginine methyl ester hydrochloride, L-368,899 did not alter the miniature excitatory postsynaptic current frequency. Thus, it is suggested that OXT-ergic neuron activity is upregulated via an increase in glutamate release, and that the upregulated OXT neurons have a feedback system with released endogenous OXT. It is possible that nitric oxide, but not GABA, may contribute to the feedback system of OXT neurons in chronic inflammation.

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.

Corticostriatal Paired-Pulse Potentiation Produced by Voltage-Dependent Activation of NMDA Receptors and L-Type Ca2+ Channels

2002 ◽  
Vol 87 (1) ◽  
pp. 157-165 ◽  
Author(s):  
Garnik Akopian ◽  
John P. Walsh
Keyword(s):  
Nmda Receptor ◽  
Nmda Receptors ◽  
Ampa Receptor ◽  
Brain Slices ◽  
Cell Voltage ◽  
Excitatory Postsynaptic Currents ◽  
Paired Pulse ◽  
Stimulation Intensity ◽  
Postsynaptic Currents ◽  
Voltage Dependent

AMPA and N-methyl-d-aspartate (NMDA) receptor-mediated synaptic responses expressed differential paired-pulse plasticity when examined in the same cell using intracellular or whole cell voltage-clamp recordings. Electrical stimulation of corticostriatal afferents in brain slices bathed in artificial cerebrospinal fluid containing bicuculline produces excitatory postsynaptic potentials and excitatory postsynaptic currents (EPSCs) mediated primarily by AMPA receptors. Cell-to-cell variation existed in AMPA receptor paired-pulse plasticity, but within-cell plasticity was stable over a range of stimulation intensities. Addition of 6-cyano-7-nitroquinoxalene-2,3-dione blocked most of the synaptic response leaving behind a small AP-5-sensitive component. Increasing the stimulation intensity produced large, long-lasting NMDA receptor-mediated responses. In contrast to AMPA receptor-mediated responses, NMDA receptor responses consistently showed an increase in paired-pulse potentiation with increasing stimulation intensity. This relationship was restricted to interstimulus intervals shorter than 100 ms. Paired-pulse potentiation of NMDA receptor responses was voltage-dependent and reduced by removal of extracellular Mg2+. Block of postsynaptic L-type Ca2+ channels with nifedipine produced a voltage-dependent reduction of NMDA receptor excitatory postsynaptic currents (EPSCs) and a voltage-dependent reduction of NMDA receptor paired-pulse potentiation. These data indicate depolarization during the first NMDA receptor response causes facilitation of the second by removing voltage-dependent block of NMDA receptors by Mg2+ and by activating voltage-dependent Ca2+ channels.

scholarly journals Vanilloid, purinergic, and CCK receptors activate glutamate release on single neurons of the nucleus tractus solitarius centralis

2011 ◽  
Vol 301 (2) ◽  
pp. R394-R401 ◽  
Author(s):  
Kirsteen N. Browning ◽  
ShuXia Wan ◽  
Vander Baptista ◽  
R. Alberto Travagli
Keyword(s):  
Nucleus Tractus Solitarius ◽  
Glutamate Release ◽  
Single Neurons ◽  
Excitatory Postsynaptic Currents ◽  
Cck Receptors ◽  
Postsynaptic Currents ◽  
C Fibers ◽  
Whole Cell Patch Clamp ◽  
Vagal Afferent ◽  
Paracrine Activation

Baroreceptor inputs to nucleus of the tractus solitarius medialis (mNTS) neurons can be differentiated, among other features, by their response to vanilloid or purinergic agonists, active only on C- or A-fibers, respectively. A major aim of this study was to examine whether neurons of NTS centralis (cNTS), a subnucleus dominated by esophageal inputs, exhibit a similar dichotomy. Since it has been suggested that cholecystokinin (CCK), exerts its gastrointestinal (GI)-related effects via paracrine activation of vagal afferent C-fibers, we tested whether CCK-sensitive fibers impinging upon cNTS neurons are responsive to vanilloid but not purinergic agonists. Using whole cell patch-clamp recordings from cNTS, we recorded miniature excitatory postsynaptic currents (mEPSCs) to test the effects of the vanilloid agonist capsaicin, the purinergic agonist α,β-methylene-ATP (α,β-Met-ATP), and/or CCK-octapeptide (CCK-8s). α,β-Met-ATP, capsaicin; and CCK-8s increased EPSC frequency in 37, 71, and 46% of cNTS neurons, respectively. Approximately 30% of cNTS neurons were responsive to both CCK-8s and α,β-Met-ATP, to CCK-8s and capsaicin, or to α,β-Met-ATP and capsaicin, while 32% of neurons were responsive to all three agonists. All neurons responding to either α,β-Met-ATP or CCK-8s were also responsive to capsaicin. Perivagal capsaicin, which is supposed to induce a selective degeneration of C-fibers, decreased the number of cNTS neurons responding to capsaicin or CCK-8s but not those responding to α,β-Met-ATP. In summary, GI inputs to cNTS neurons cannot be distinguished on the basis of their selective responses to α,β-Met-ATP or capsaicin. Our data also indicate that CCK-8s increases glutamate release from purinergic and vanilloid responsive fibers impinging on cNTS neurons.

Hippocampal inhibitory interneurons are functionally disconnected from excitatory inputs by anoxia

1993 ◽  
Vol 70 (6) ◽  
pp. 2251-2259 ◽  
Author(s):  
R. Khazipov ◽  
P. Bregestovski ◽  
Y. Ben-Ari
Keyword(s):  
Pyramidal Neurons ◽  
Hippocampal Slices ◽  
Pyramidal Cells ◽  
Gabab Receptors ◽  
Stratum Radiatum ◽  
Gamma Aminobutyric Acid ◽  
Patch Clamp Recording ◽  
Synaptic Currents ◽  
Postsynaptic Currents ◽  
Whole Cell Patch Clamp

1. The effects of anoxia on inhibitory synaptic transmission were studied in hippocampal slices of 3- to 4-wk-old rats. CA1 pyramidal cells were examined by whole-cell patch-clamp recording. Synaptic currents were evoked by “distant” (> 0.5 mm) or “close” (< 0.5 mm) electrical stimulation in the stratum radiatum. 2. The excitatory postsynaptic currents (EPSCs) and inhibitory postsynaptic currents (IPSCs) evoked by distant stimulation were completely suppressed by brief anoxia (95% N2-5% CO2 for 4-6 min) and recovered upon reoxygenation. IPSCs were more sensitive to anoxia than EPSCs. EPSCs and IPSCs evoked by distant stimulation were blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 20 microM) and D-2-amino-5-phosphonopentanoate (APV; 50 microM). This indicates that IPSCs were mediated via a polysynaptic pathway that involves glutamate receptors. 3. Synaptic currents evoked by close stimulation were only partly inhibited by anoxia. The bicuculline-sensitive gamma-aminobutyric acid-A (GABAA) receptor-mediated synaptic currents were particularly resistant to anoxia, suggesting that the GABAergic input to pyramidal neurons is not inhibited by anoxia. 4. At close stimulation in the stratum radiatum, monosynaptic IPSCs could be evoked in the presence of CNQX (20 microM) and APV (50 microM). The monosynaptic IPSCs had early bicuculline (15 microM) and late CGP 35348 (100 microM)-sensitive components confirming an involvement of GABAA and GABAB receptors (IPSCA and IPSCB components), respectively. 5. The monosynaptic IPSCA component evoked by close stimulation was not changed significantly during and after brief anoxia. Responses to pressure application of isoguvacine (GABAA agonist) were also not affected by anoxia.(ABSTRACT TRUNCATED AT 250 WORDS)

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