Enhancement of Excitatory Synaptic Transmission in Spiny Neurons After Transient Forebrain Ischemia

2006 ◽  
Vol 95 (3) ◽  
pp. 1537-1544 ◽  
Author(s):  
Yuchun Zhang ◽  
Ping Deng ◽  
Yan Li ◽  
Zao C. Xu
Keyword(s):  
Pyridoxal Phosphate ◽  
Glutamate Release ◽  
P2x Receptor ◽  
Disulfonic Acid ◽  
Forebrain Ischemia ◽  
Excitatory Postsynaptic Currents ◽  
Transient Forebrain Ischemia ◽  
Postsynaptic Currents ◽  
Spiny Neurons ◽  
Presynaptic Mechanisms

Spiny neurons in the neostriatum are highly vulnerable to ischemia. Enhancement of excitatory synaptic transmissions has been implicated in ischemia-induced excitotoxic neuronal death. Here we report that evoked excitatory postsynaptic currents in spiny neurons were potentiated after transient forebrain ischemia. The ischemia-induced potentiation in synaptic efficacy was associated with an enhancement of presynaptic release as demonstrated by an increase in the frequency of miniature excitatory postsynaptic currents (mEPSCs) and a decrease in the paired-pulse ratio. The amplitude of inward currents evoked by exogenous application of glutamate did not show significant changes after ischemia, suggesting that postsynaptic mechanism is not involved. The ischemia-induced increase in mEPSCs frequency was not affected by blockade of voltage-gated calcium channels, but it was eliminated in the absence of extracellular calcium. Bath application of ATP P2X receptor antagonist pyridoxal-phosphate-6-azophenyl-2′,4′-disulfonic acid (PPADS) significantly reduced mEPSC frequency in ischemic neurons but had no effects on the control ones. Furthermore, the inhibitory effect of PPADS on ischemic neurons was abolished in Ca2+-free external solution. These results indicate that excitatory synaptic transmissions in spiny neurons are potentiated after ischemia via presynaptic mechanisms. Activation of P2X receptors and the consequent Ca2+ influx might contribute to the ischemia-induced facilitation of glutamate release.

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 <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.

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.

An adenosine uptake blocker, propentofylline, reduces glutamate release in gerbil hippocampus following transient forebrain ischemia

1992 ◽  
Vol 17 (2) ◽  
pp. 147-150 ◽  
Author(s):  
Kotaro Miyashita ◽  
Takashi Nakajima ◽  
Atsushi Ishikawa ◽  
Tadashi Miyatake
Keyword(s):  
Glutamate Release ◽  
Forebrain Ischemia ◽  
Transient Forebrain Ischemia ◽  
Adenosine Uptake

scholarly journals Cloning and characterization of a functional P2X receptor from larval bullfrog skin

2001 ◽  
Vol 281 (3) ◽  
pp. C954-C962 ◽  
Author(s):  
Philip J. Jensik ◽  
Doyle Holbird ◽  
Michael W. Collard ◽  
Thomas C. Cox
Keyword(s):  
Pyridoxal Phosphate ◽  
Rana Catesbeiana ◽  
Short Circuit ◽  
Short Circuit Current ◽  
P2x Receptors ◽  
P2x Receptor ◽  
Disulfonic Acid ◽  
Acid Protein ◽  
Sensory Reception ◽  
Tadpole Skin

ATP activates an apical-to-basolateral nonselective cation current across the skin of larval bullfrogs ( Rana catesbeiana) with similarities to currents carried by some P2X receptors. A functional P2X receptor was cloned from tadpole skin RNA that encodes a 409-amino acid protein with highest protein homology to cP2X8. RT-PCR showed that this transcript was found in skin, heart, eye, brain, and skeletal muscle of tadpoles but not in skin, brain, or heart of adults. After transcribed RNA from this clone was injected into Xenopus oocytes, application of ATP activated a transient current similar to other P2X receptors and the ATP-activated transient in short-circuit current ( I sc) across intact skin. The agonists 2-methylthio-ATP and adenosine-5′- O-(thiotriphoshate) also activated transient currents. α,β-Methylene-ATP and ADP were poor agonists of this receptor. Suramin and pyridoxal phosphate 6-azophenyl-2′,4′-disulfonic acid tetrasodium (PPADS) were potent antagonists, and PPADS showed an irreversible blockade of this receptor to agonist activation. Under external Na+-free, Ca2+/Mg2+-free conditions ( N-methyl-d-glucamine replacement, 0.5 mM EGTA), ATP activated a steadily increasing inward current. Fluorescence microscopy showed that propidium was entering the cells, suggesting that a relatively large pore size was formed under zero divalent conditions. This clone has some characteristics consistent with previously described ATP-activated I sc in the tadpole skin. Because the clone is not found in adult skin, it may have some exclusive role in the tadpole such as sensory reception by the skin or triggering apoptosis at metamorphosis.

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.

scholarly journals Effect of nitric oxide synthase inhibitor on striatum glutamate release in rat transient forebrain ischemia.

Nosotchu ◽  
1994 ◽  
Vol 16 (2) ◽  
pp. 102-108 ◽  
Author(s):  
Kazunori Nanri ◽  
Shunya Takizawa ◽  
Hitoshi Fujita ◽  
Saori Ogawa ◽  
Yukito Shinohara
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Glutamate Release ◽  
Forebrain Ischemia ◽  
Nitric Oxide Synthase Inhibitor ◽  
Transient Forebrain Ischemia ◽  
Synthase Inhibitor ◽  
Oxide Synthase

Do P2X purinergic receptors regulate skeletal muscle blood flow during exercise?

2004 ◽  
Vol 286 (2) ◽  
pp. H633-H639 ◽  
Author(s):  
John B. Buckwalter ◽  
Jessica C. Taylor ◽  
Jason J. Hamann ◽  
Philip S. Clifford
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Femoral Artery ◽  
Purinergic Receptors ◽  
Pyridoxal Phosphate ◽  
Muscle Blood Flow ◽  
Sympathetic Nerves ◽  
P2x Receptor ◽  
Disulfonic Acid ◽  
Skeletal Muscle Blood Flow

Although there is evidence that sympathetic nerves release ATP as a neurotransmitter to produce vasoconstriction via P2X purinergic receptors, the role of these receptors in the regulation of blood flow to exercising skeletal muscle has yet to be determined. We hypothesized that there is tonic P2X receptor-mediated vasoconstriction in exercising skeletal muscle. To test this hypothesis, the effect of P2X receptor blockade on skeletal muscle blood flow was examined in six exercising mongrel dogs. P2X receptor antagonism was accomplished with pyridoxal-phosphate-6-azophenyl-2′4′-disulfonic acid (PPADs). Animals were instrumented chronically with flow probes on the external iliac arteries of both hindlimbs and a catheter in one femoral artery. PPADs (40 mg) was infused as a bolus into the femoral artery catheter during steady-state exercise at 6 miles/h. Intra-arterial infusion of PPADs increased iliac blood flow from 542 ± 55 to 677 ± 69 ml/min ( P < 0.05) and iliac vascular conductance from 5.17 ± 0.62 to 6.53 ± 0.80 ml·min–1·mmHg–1. The PPADs infusion did not affect blood flow in the contralateral iliac artery. These data support the hypothesis that P2X purinergic receptors produce vasoconstriction in exercising skeletal muscle.

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