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丘脑神经元中γ-氨基丁酸B型受体依赖性爆发式放电:一项动态钳研究

Gamma-aminobutyric acid type B receptor-dependent burst-firing in thalamic neurons: a dynamic clamp study.

作者信息

Ulrich D, Huguenard J R

机构信息

Department of Neurology and Neurological Sciences, Stanford University School of Medicine, CA 94305-5300, USA.

出版信息

Proc Natl Acad Sci U S A. 1996 Nov 12;93(23):13245-9. doi: 10.1073/pnas.93.23.13245.

Abstract

Synchronized network responses in thalamus depend on phasic inhibition originating in the thalamic reticular nucleus (nRt) and are mediated by the neurotransmitter gamma-aminobutyric acid (GABA). A suggested role for intra-nRt connectivity in inhibitory phasing remains controversial. Recently, functional GABA type B (GABAB) receptors were demonstrated on nRt cells, and the slow time course of the GABAB synaptic response seems ideally suited to deinactivate low-threshold calcium channels. This promotes burst firing, a characteristic feature of synchronized responses. Here we investigate GABAB-mediated rebound burst firing in thalamic cells. Whole-cell current-clamp recordings were obtained from nRt cells and somatosensory thalamocortical relay cells in rat brain slices. Synthetic GABAB inhibitory postsynaptic potentials, generated by a hybrid computerneuron synapse (dynamic clamp), triggered rebound low-threshold calcium spikes in both cell types when peak inhibitory postsynaptic potential hyperpolarization was greater than -92 mV. The threshold inhibitory postsynaptic potential conductance for rebound burst generation was comparable in nRt (7 nS) and thalamocortical (5 nS) cells. However, burst onset in nRt (1 s) was considerably delayed compared with thalamocortical (0.6 s) cells. Thus, GABAB inhibitory postsynaptic potentials can elicit low-threshold calcium spikes in both relay and nRt neurons, but the resultant oscillation frequency would be faster for thalamocortical-nRt networks (3 Hz) than for nRt-nRt networks (1-2 Hz). We conclude, therefore, that fast (> 2 Hz) GABAB-dependent thalamic oscillations are maintained primarily by reciprocal connections between excitatory and inhibitory cells. These findings further indicate that when oscillatory neural networks contain both recurrent and reciprocal inhibition, then distinct population frequencies may result when one or the other type of inhibition is favored.

摘要

丘脑的同步网络反应依赖于起源于丘脑网状核(nRt)的相位抑制,并由神经递质γ-氨基丁酸(GABA)介导。nRt内连接在抑制相位中的假定作用仍存在争议。最近,在nRt细胞上发现了功能性GABA B型(GABAB)受体,并且GABAB突触反应的缓慢时间进程似乎非常适合使低阈值钙通道失活。这促进了爆发式放电,这是同步反应的一个特征。在这里,我们研究了丘脑细胞中GABAB介导的反弹爆发式放电。在大鼠脑片上从nRt细胞和体感丘脑皮质中继细胞获得全细胞电流钳记录。当峰值抑制性突触后电位超极化大于-92 mV时,由混合计算机-神经元突触(动态钳)产生的合成GABAB抑制性突触后电位在两种细胞类型中均触发了反弹低阈值钙峰。nRt(7 nS)和丘脑皮质(5 nS)细胞中产生反弹爆发的阈值抑制性突触后电位电导相当。然而,与丘脑皮质(0.6 s)细胞相比,nRt(1 s)中的爆发起始明显延迟。因此,GABAB抑制性突触后电位可在中继神经元和nRt神经元中引发低阈值钙峰,但丘脑皮质-nRt网络(3 Hz)产生的振荡频率比nRt-nRt网络(1-2 Hz)更快。因此,我们得出结论,快速(>2 Hz)的依赖GABAB的丘脑振荡主要由兴奋性和抑制性细胞之间的相互连接维持。这些发现进一步表明,当振荡神经网络同时包含递归抑制和相互抑制时,当一种或另一种类型的抑制占优势时,可能会产生不同的群体频率。

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