Physiological evidence for local excitatory synaptic circuits in the rat hypothalamus
Physiological evidence for local excitatory synaptic circuits in the rat hypothalamus
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DOI：
10.1152/jn.1997.77.6.3396
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发表时间：
1997-06-01
影响因子：
2.5
通讯作者：
Tasker, JG
中科院分区：
文献类型：
--
作者：
Boudaba, C;Schrader, LA;Tasker, JG
采用全细胞电压钳和电流钳技术在大鼠下丘脑脑片上记录局部兴奋性突触回路。用电刺激和化学刺激研究了室旁核（PVN）和视上核（SON）神经元的局部兴奋性输入。细胞外电刺激提供了局部兴奋回路的间接证据。单次刺激在某些PVN和SON细胞中诱发多个兴奋性突触后电位（EPSP）或兴奋性突触后电流（EPSC），引起多突触兴奋性输入。重复刺激（10-20 Hz，2-10 s）引起EPSP/EPSC的长后放电，表明多突触回路中上游突触的增强。代谢型谷氨酸受体激动剂的水浴应用为局部兴奋回路提供了更确凿的证据。代谢型受体激活引起的EPSP/EPSC的频率增加，被河豚毒素阻断，这表明它是由激活局部突触前兴奋性神经元介导的。SON和PVN神经元的局部兴奋性输入由谷氨酸释放介导，因为电刺激和代谢型受体激活引起的EPSP/EPSC被离子型谷氨酸受体拮抗剂阻断。最后，谷氨酸微刺激提供了最直接的演示局部兴奋性突触回路。谷氨酸微刺激核周位点引起的EPSP/EPSC的频率增加，在13%的PVN和SON神经元测试。两个网站提供了大部分的本地兴奋性突触输入PVN神经元，背内侧下丘脑和穹窿周围区。这些实验提供了收敛的生理证据，局部兴奋性突触输入下丘脑神经元，输入可能在脉冲激素释放中发挥作用。
We conducted whole cell voltage-clamp and current-clamp recordings ill slices of rat hypothalamus to test for local excitatory synaptic circuits. Local excitatory inputs to neurons of the paraventricular nucleus (PVN) and supraoptic nucleus (SON) were studied with the use of electrical and chemical stimulation. Extracellular electrical stimulation provided indirect evidence of local excitatory circuits. Single stimuli evoked multiple excitatory postsynaptic potentials (EPSPs) or excitatory postsynaptic currents (EPSCs) in some PVN and SON cells, invoking polysynaptic excitatory inputs. Repetitive stimulation (10-20 Hz, 2-10 s) elicited long afterdischarges of EPSPs/EPSCs suggesting a potentiation of upstream synapses in a polysynaptic circuit. Bath application of metabotropic glutamate receptor agonists provided more conclusive evidence for local excitatory circuits. Metabotropic receptor activation caused an increase in the frequency of EPSPs/EPSCs that was blocked by tetrodotoxin, suggesting that it was mediated by activation of local presynaptic excitatory neurons. The local excitatory inputs to SON and PVN neurons were mediated by glutamate release, because the EPSPs/EPSCs elicited with electrical stimulation and metabotropic receptor activation were blocked by ionotropic glutamate receptor antagonists. Finally, glutamate microstimulation furnished the most direct demonstration of local excitatory synaptic circuits. Glutamate microstimulation of perinuclear sites elicited an increase in the frequency of EPSPs/EPSCs in 13% of the PVN and SON neurons tested. Two sites provided most of the local excitatory synaptic inputs to PVN neurons, the dorsomedial hypothalamus and the perifornical region. These experiments provide converging physiological evidence for local excitatory synaptic inputs to hypothalamic neurons, inputs that may play a role in pulsatile hormone release.