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
The γ-aminobutyric acid neurotransmitter in the spinal cord dorsal horn plays an important role in pain modulation through primary afferent-mediated presynaptic inhibition. The weakening of γ-aminobutyric acid-media...The γ-aminobutyric acid neurotransmitter in the spinal cord dorsal horn plays an important role in pain modulation through primary afferent-mediated presynaptic inhibition. The weakening of γ-aminobutyric acid-mediated presynaptic inhibition may be an important cause of neuropathic pain. γ-aminobutyric acid-mediated presynaptic inhibition is related to the current strength of γ-aminobutyric acid A receptor activation. In view of this, the whole-cell patch-clamp technique was used here to record the change in muscimol activated current of dorsal root ganglion neurons in a chronic constriction injury model. Results found that damage in rat dorsal root ganglion neurons following application of muscimol caused concentration-dependent activation of current, and compared with the sham group, its current strength and γ-aminobutyric acid A receptor protein expression decreased. Immunofluorescence revealed that γ-aminobutyric acid type A receptor α2 subunit protein expression decreased and was most obvious at 12 and 15 days after modeling. Our experimental findings confirmed that the y-aminobutyric acid type A receptor α2 subunit in the chronic constriction injury model rat dorsal root ganglion was downregulated, which may be one of the reasons for the reduction of injury in dorsal root ganglion neurons following muscimol-activated currents.展开更多
目的探讨β2-烟碱型乙酰胆碱受体(β2-n ACh R)在海马CA1和CA3锥体神经元的A型γ-氨基丁酸受体(GABA_A-R)发育中的作用。方法应用β2-n ACh R基因敲除小鼠(β2-KO组)制备急性分离的海马CA1和CA3锥体神经元,应用穿孔膜片钳记录技术记录GA...目的探讨β2-烟碱型乙酰胆碱受体(β2-n ACh R)在海马CA1和CA3锥体神经元的A型γ-氨基丁酸受体(GABA_A-R)发育中的作用。方法应用β2-n ACh R基因敲除小鼠(β2-KO组)制备急性分离的海马CA1和CA3锥体神经元,应用穿孔膜片钳记录技术记录GABA_A-R选择性激动剂蝇蕈醇在CA1和CA3锥体神经元诱导的GABA电流,测试其平衡电位(E_(Mus))和动力学指标,并与野生型小鼠(WT组)进行比较。结果β2-KO组小鼠(n=4)CA1锥体神经元(n=7)的E_(Mus)为-31.7±3.5 m V,与WT组相比向去极化偏移(P<0.05);CA3锥体神经元(n=4)的E_(Mus)为-16.1±4.6 m V,同样较WT组偏向去极化方向(P<0.01);与WT组小鼠不同,β2-KO组小鼠CA3和CA1神经元的E_(Mus)差异有统计学意义(P<0.05)。β2-KO组小鼠CA1和CA3神经元上都显示GABA_A-R的失敏显著减慢,衰减时间分别为2.2±0.2 s、3.2±0.1 s(WT组为1.6±0.1 s、2.3±0.1 s,P<0.05或P<0.01)。结论含β2的n ACh R可能参与促进小鼠海马CA1和CA3锥体细胞中GABA_A-R的功能成熟。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
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
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 Youth Science and Technology Innovation Special Foundation of Xinjiang Production and Construction Corps, China, No. 2010JC33
文摘The γ-aminobutyric acid neurotransmitter in the spinal cord dorsal horn plays an important role in pain modulation through primary afferent-mediated presynaptic inhibition. The weakening of γ-aminobutyric acid-mediated presynaptic inhibition may be an important cause of neuropathic pain. γ-aminobutyric acid-mediated presynaptic inhibition is related to the current strength of γ-aminobutyric acid A receptor activation. In view of this, the whole-cell patch-clamp technique was used here to record the change in muscimol activated current of dorsal root ganglion neurons in a chronic constriction injury model. Results found that damage in rat dorsal root ganglion neurons following application of muscimol caused concentration-dependent activation of current, and compared with the sham group, its current strength and γ-aminobutyric acid A receptor protein expression decreased. Immunofluorescence revealed that γ-aminobutyric acid type A receptor α2 subunit protein expression decreased and was most obvious at 12 and 15 days after modeling. Our experimental findings confirmed that the y-aminobutyric acid type A receptor α2 subunit in the chronic constriction injury model rat dorsal root ganglion was downregulated, which may be one of the reasons for the reduction of injury in dorsal root ganglion neurons following muscimol-activated currents.
文摘目的探讨β2-烟碱型乙酰胆碱受体(β2-n ACh R)在海马CA1和CA3锥体神经元的A型γ-氨基丁酸受体(GABA_A-R)发育中的作用。方法应用β2-n ACh R基因敲除小鼠(β2-KO组)制备急性分离的海马CA1和CA3锥体神经元,应用穿孔膜片钳记录技术记录GABA_A-R选择性激动剂蝇蕈醇在CA1和CA3锥体神经元诱导的GABA电流,测试其平衡电位(E_(Mus))和动力学指标,并与野生型小鼠(WT组)进行比较。结果β2-KO组小鼠(n=4)CA1锥体神经元(n=7)的E_(Mus)为-31.7±3.5 m V,与WT组相比向去极化偏移(P<0.05);CA3锥体神经元(n=4)的E_(Mus)为-16.1±4.6 m V,同样较WT组偏向去极化方向(P<0.01);与WT组小鼠不同,β2-KO组小鼠CA3和CA1神经元的E_(Mus)差异有统计学意义(P<0.05)。β2-KO组小鼠CA1和CA3神经元上都显示GABA_A-R的失敏显著减慢,衰减时间分别为2.2±0.2 s、3.2±0.1 s(WT组为1.6±0.1 s、2.3±0.1 s,P<0.05或P<0.01)。结论含β2的n ACh R可能参与促进小鼠海马CA1和CA3锥体细胞中GABA_A-R的功能成熟。
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.
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.
