Objective To examine the effects of urotensin Ⅱ （UⅡ） on the discharges of neurons in CA1 area of hippocampal slices by using extracellular recording technique. Results ①In response to the application of UⅡ （0.3...Objective To examine the effects of urotensin Ⅱ （UⅡ） on the discharges of neurons in CA1 area of hippocampal slices by using extracellular recording technique. Results ①In response to the application of UⅡ （0.3, 3.0, 30.0,300.0 nmol/L, n = 77） into the perfusate for 2 min, the spontaneous discharge rates （SDR） of 63/77 （81.8% ） neurons were significantly decreased in a dose-dependent manner. ②Pretreatment with bicuculline（BIC, 100 μmol/L）, a specific GABAs receptor antagonist, led to a marked increase in the SDR of 6/7 （85.71%） neurons in an epileptiform pattern. The increased discharges were not significantly changed after UⅡ （30.0 nmol/L） was applied into the perfusate for 2 min. ③Pretreatment with picrotoxin （ PIC, 50 μmol/L）, a selective blocker of Cl^- channel, led to an increase in the SDR of all 8/8（ 100% ） neurons. The increased discharges were not influenced by the UⅡ （30.0 nmol/L） applied. ④Application of nitric oxide synthase （NOS） inhibitor N^G nitro-L-arginine methyl ester （L-NAME, 50μmol/L） into the perfusate for 2 min also significantly augmented the SDR of 14/16 （87.5 % ） neurons , then UⅡ （30.0 nmol/L） applied into the perfusate reduced the increased the SDR of all 14/14 （ 100% ） neurons. Conclusion These results suggest that UⅡ may decrease neuronal activity by potentiating GABAA receptor-mediated CI current in hippocampal CA1 neurons, and involved with the mediation of nitric oxide.展开更多
The effects of electrical stimulation of second somatosensory area(S Ⅱ)andelectroacupuncture(EA)at Huantiao(GB 30)and Yanglinquan(GB 34)points on nociceptive re-sponses of neurons in the nucleus centrum medianum(CM)i...The effects of electrical stimulation of second somatosensory area(S Ⅱ)andelectroacupuncture(EA)at Huantiao(GB 30)and Yanglinquan(GB 34)points on nociceptive re-sponses of neurons in the nucleus centrum medianum(CM)in the thalamus were respectively ob-served after topical application of bicuculline(Bic)at the motor cortex(MCtx),and the results werecompared with those obtained in the saline control group.It was found that following application ofBic either electrical stimulation of SII(n=11)or EA(n=11)yielded obvious inhibition on nocicep-tive responses of CM neurons(P【0.05),which was similar to the inhibitory effects obtained in thesaline control groups(n=11,n=10).After GABA application at MCtx electrical stimulation of SIIfailed to show inhibition on nociceptive responses in 3 CM neurons.It is indicated that GABA in MC-tx is involved in SII originating corticofugal regulation of nucleus CM in acupuncture analgesia.展开更多
Presynaptic modulation Of [3H] GABA release was examined using rat cerebral cortical slices. In vitro addition of muscimol, a GABAA receptor agonist, resulted in a significant suppression of the release of [3H] GABA e...Presynaptic modulation Of [3H] GABA release was examined using rat cerebral cortical slices. In vitro addition of muscimol, a GABAA receptor agonist, resulted in a significant suppression of the release of [3H] GABA evoked evoked by high potassium stimulation in a dose dependent manner, whereas beclofen, a GABAB receptor agonist, had no significant effect on the release. Furthermore, it was found that the suppressive effect of muscimol could be antagonized invariably by bicuculline, a GABAA receptor antagonist. These results suggest that the release of [3H] GABA from rat cerebral conical GABA neurous may be modulated by presynaptic GABAA autoreceptor.展开更多
This work examines the influence of Cl- (2.5 - 125 mM) and HCO3- (2 - 30 mM) on the Cl-/HCO3- - ATPase complex of the neuronal membrane and this enzyme is a Cl--pump that is coupled to GABAA receptors. The greatest (4...This work examines the influence of Cl- (2.5 - 125 mM) and HCO3- (2 - 30 mM) on the Cl-/HCO3- - ATPase complex of the neuronal membrane and this enzyme is a Cl--pump that is coupled to GABAA receptors. The greatest (44%) activating effect on the enzyme is found with HCO3- (20 - 30 mM), while the maximum activity occurs in the presence of a ratio of ~25 mM HCO3- /~5mM Cl-. Blockers of the GABAA receptor, namely bicuculline (10 - 50 μM) and picrotoxin (50 - 100 μM), inhibit this anion activation, whereas the HCO3- -ATPase activity is not sensitive to these ligands. Autoradiographic analysis of the spectrum of the partially purified enzyme phosphorylated with [γ-32P]ATP allowed us to distinguish three major 32P-labeled protein whose molecular weight are about 57, 53, and 48 kDa. In the presence of 5 mM Cl-/25mM HCO3- and 100 μM picrotoxin, the intensity of the phosphorylation of bands significantly decreased, thereby confirming the assumption about coupled of binding sites for anions and GABAA-ergic ligands. It was suggested scheme of Cl--transport through the plasma membrane by utilizing neuronal Cl-/ -HCO3- ATPase in the low (5 mM) Cl- and high (25 mM) HCO3- concentrations. The data demonstrated for the first time that the GABAA-coupled Cl-/ HCO3- -ATPase from rat brain neuronal membranes is maximally activated at a Cl-/HCO3- ratio of 1:5 and it remains stable at high concentrations of substrate and buffer.展开更多
Exploring the transition from inter-ictal to ictal epileptiform discharges(IDs) and how GABAAreceptormediated action affects the onset of IDs will enrich our understanding of epileptogenesis and epilepsy treatment.We ...Exploring the transition from inter-ictal to ictal epileptiform discharges(IDs) and how GABAAreceptormediated action affects the onset of IDs will enrich our understanding of epileptogenesis and epilepsy treatment.We used Mg2+-free artificial cerebrospinal fluid(ACSF) to induce epileptiform discharges in juvenile mouse hippocampal slices and used a micro-electrode array to record the discharges. After the slices were exposed to Mg2+-free ACSF for 10 min–20 min, synchronous recurrent seizurelike events were recorded across the slices, and each event evolved from inter-ictal epileptiform discharges(IIDs) to pre-ictal epileptiform discharges(PIDs), and then to IDs.During the transition from IIDs to PIDs, the duration of discharges increased and the inter-discharge interval decreased. After adding 3 lmol/L of the GABAAreceptor agonist muscimol, PIDs and IDs disappeared, and IIDs remained. Further, the application of 10 lmol/L muscimol abolished all the epileptiform discharges. When the GABAAreceptor antagonist bicuculline was applied at 10 lmol/L, IIDs and PIDs disappeared, and IDs remained at decreased intervals. These results indicated that there are dynamic changes in the hippocampal network preceding the onset of IDs, and GABAAreceptor activity suppresses the transition from IIDs to IDs in juvenile mouse hippocampus.展开更多
In this study we investigated whether GABAA receptors of the basolateral amygdala(BLA) interact with the effect of dexamethasone on the retrieval stage of memory.Adult male Wistar rats were bilaterally cannulated in t...In this study we investigated whether GABAA receptors of the basolateral amygdala(BLA) interact with the effect of dexamethasone on the retrieval stage of memory.Adult male Wistar rats were bilaterally cannulated in the BLA by stereotaxic surgery.The animals were trained in step-through apparatus by induction of electric shock(1.5 mA,3 s) and were tested for memory retrieval after 1 d.The time of latency for entering the dark compartment of the instrument and the time spent by rats in this chamber were recorded for evaluation of the animals' retrieval in passive avoidance memory.Administration of dexamethasone(0.3 and 0.9 mg/kg,subcutaneously(s.c.)),immediately after training,enhanced memory retrieval.This effect was reduced by intra-BLA microinjection of muscimol(0.125,0.250 and 0.500 μg/rat),when administered before 0.9 mg/kg of dexamethasone.Microinjection of bicuculline(0.75 μg/rat,intra-BLA) with an ineffective dose of dexamethasone(0.1 mg/kg,s.c.) increased memory retrieval.However,the same doses of muscimol and bicuculline without dexamethasone did not affect memory processes.Our data support reports that dexamethasone enhances memory retrieval.It seems that GABAA receptors of the BLA mediate the effect of dexamethasone on memory retrieval in rats.展开更多
文摘Objective To examine the effects of urotensin Ⅱ （UⅡ） on the discharges of neurons in CA1 area of hippocampal slices by using extracellular recording technique. Results ①In response to the application of UⅡ （0.3, 3.0, 30.0,300.0 nmol/L, n = 77） into the perfusate for 2 min, the spontaneous discharge rates （SDR） of 63/77 （81.8% ） neurons were significantly decreased in a dose-dependent manner. ②Pretreatment with bicuculline（BIC, 100 μmol/L）, a specific GABAs receptor antagonist, led to a marked increase in the SDR of 6/7 （85.71%） neurons in an epileptiform pattern. The increased discharges were not significantly changed after UⅡ （30.0 nmol/L） was applied into the perfusate for 2 min. ③Pretreatment with picrotoxin （ PIC, 50 μmol/L）, a selective blocker of Cl^- channel, led to an increase in the SDR of all 8/8（ 100% ） neurons. The increased discharges were not influenced by the UⅡ （30.0 nmol/L） applied. ④Application of nitric oxide synthase （NOS） inhibitor N^G nitro-L-arginine methyl ester （L-NAME, 50μmol/L） into the perfusate for 2 min also significantly augmented the SDR of 14/16 （87.5 % ） neurons , then UⅡ （30.0 nmol/L） applied into the perfusate reduced the increased the SDR of all 14/14 （ 100% ） neurons. Conclusion These results suggest that UⅡ may decrease neuronal activity by potentiating GABAA receptor-mediated CI current in hippocampal CA1 neurons, and involved with the mediation of nitric oxide.
基金This project is supported by National Natural Science Fundation of China
文摘The effects of electrical stimulation of second somatosensory area(S Ⅱ)andelectroacupuncture(EA)at Huantiao(GB 30)and Yanglinquan(GB 34)points on nociceptive re-sponses of neurons in the nucleus centrum medianum(CM)in the thalamus were respectively ob-served after topical application of bicuculline(Bic)at the motor cortex(MCtx),and the results werecompared with those obtained in the saline control group.It was found that following application ofBic either electrical stimulation of SII(n=11)or EA(n=11)yielded obvious inhibition on nocicep-tive responses of CM neurons(P【0.05),which was similar to the inhibitory effects obtained in thesaline control groups(n=11,n=10).After GABA application at MCtx electrical stimulation of SIIfailed to show inhibition on nociceptive responses in 3 CM neurons.It is indicated that GABA in MC-tx is involved in SII originating corticofugal regulation of nucleus CM in acupuncture analgesia.
文摘Presynaptic modulation Of [3H] GABA release was examined using rat cerebral cortical slices. In vitro addition of muscimol, a GABAA receptor agonist, resulted in a significant suppression of the release of [3H] GABA evoked evoked by high potassium stimulation in a dose dependent manner, whereas beclofen, a GABAB receptor agonist, had no significant effect on the release. Furthermore, it was found that the suppressive effect of muscimol could be antagonized invariably by bicuculline, a GABAA receptor antagonist. These results suggest that the release of [3H] GABA from rat cerebral conical GABA neurous may be modulated by presynaptic GABAA autoreceptor.
文摘This work examines the influence of Cl- (2.5 - 125 mM) and HCO3- (2 - 30 mM) on the Cl-/HCO3- - ATPase complex of the neuronal membrane and this enzyme is a Cl--pump that is coupled to GABAA receptors. The greatest (44%) activating effect on the enzyme is found with HCO3- (20 - 30 mM), while the maximum activity occurs in the presence of a ratio of ~25 mM HCO3- /~5mM Cl-. Blockers of the GABAA receptor, namely bicuculline (10 - 50 μM) and picrotoxin (50 - 100 μM), inhibit this anion activation, whereas the HCO3- -ATPase activity is not sensitive to these ligands. Autoradiographic analysis of the spectrum of the partially purified enzyme phosphorylated with [γ-32P]ATP allowed us to distinguish three major 32P-labeled protein whose molecular weight are about 57, 53, and 48 kDa. In the presence of 5 mM Cl-/25mM HCO3- and 100 μM picrotoxin, the intensity of the phosphorylation of bands significantly decreased, thereby confirming the assumption about coupled of binding sites for anions and GABAA-ergic ligands. It was suggested scheme of Cl--transport through the plasma membrane by utilizing neuronal Cl-/ -HCO3- ATPase in the low (5 mM) Cl- and high (25 mM) HCO3- concentrations. The data demonstrated for the first time that the GABAA-coupled Cl-/ HCO3- -ATPase from rat brain neuronal membranes is maximally activated at a Cl-/HCO3- ratio of 1:5 and it remains stable at high concentrations of substrate and buffer.
基金supported by the Key Basic Research Project of Science and Technology Commission of Shanghai (13DJ1400303)the Shanghai Jiao Tong University Fund for Interdisciplinary Research for Medical Applications (YG2012ZD08)the Seed Fund of Ren Ji Hospital (RJ ZZ13-005)
文摘Exploring the transition from inter-ictal to ictal epileptiform discharges(IDs) and how GABAAreceptormediated action affects the onset of IDs will enrich our understanding of epileptogenesis and epilepsy treatment.We used Mg2+-free artificial cerebrospinal fluid(ACSF) to induce epileptiform discharges in juvenile mouse hippocampal slices and used a micro-electrode array to record the discharges. After the slices were exposed to Mg2+-free ACSF for 10 min–20 min, synchronous recurrent seizurelike events were recorded across the slices, and each event evolved from inter-ictal epileptiform discharges(IIDs) to pre-ictal epileptiform discharges(PIDs), and then to IDs.During the transition from IIDs to PIDs, the duration of discharges increased and the inter-discharge interval decreased. After adding 3 lmol/L of the GABAAreceptor agonist muscimol, PIDs and IDs disappeared, and IIDs remained. Further, the application of 10 lmol/L muscimol abolished all the epileptiform discharges. When the GABAAreceptor antagonist bicuculline was applied at 10 lmol/L, IIDs and PIDs disappeared, and IDs remained at decreased intervals. These results indicated that there are dynamic changes in the hippocampal network preceding the onset of IDs, and GABAAreceptor activity suppresses the transition from IIDs to IDs in juvenile mouse hippocampus.
基金supported by the Shahid Chamran University of Ahvaz,Iran
文摘In this study we investigated whether GABAA receptors of the basolateral amygdala(BLA) interact with the effect of dexamethasone on the retrieval stage of memory.Adult male Wistar rats were bilaterally cannulated in the BLA by stereotaxic surgery.The animals were trained in step-through apparatus by induction of electric shock(1.5 mA,3 s) and were tested for memory retrieval after 1 d.The time of latency for entering the dark compartment of the instrument and the time spent by rats in this chamber were recorded for evaluation of the animals' retrieval in passive avoidance memory.Administration of dexamethasone(0.3 and 0.9 mg/kg,subcutaneously(s.c.)),immediately after training,enhanced memory retrieval.This effect was reduced by intra-BLA microinjection of muscimol(0.125,0.250 and 0.500 μg/rat),when administered before 0.9 mg/kg of dexamethasone.Microinjection of bicuculline(0.75 μg/rat,intra-BLA) with an ineffective dose of dexamethasone(0.1 mg/kg,s.c.) increased memory retrieval.However,the same doses of muscimol and bicuculline without dexamethasone did not affect memory processes.Our data support reports that dexamethasone enhances memory retrieval.It seems that GABAA receptors of the BLA mediate the effect of dexamethasone on memory retrieval in rats.
