丘脑网状核团的GABA能抑制信号，通过频率依赖性的调控腹侧基底丘脑的放电模式，参与慢性炎症痛

The ventrobasal (VB) thalamus is innervated by GABAergic afferents from the thalamic reticular nucleus (TRN) and participates in nociception. The VB and TRN are in anatomically strategic positions to modulate the flow of information between the cortex and thalamus. Our previous work had found that reduced TRN-VB GABAergic transmission contributed chronic inflammatory pain. However, the network-level mechanisms that link its activity to VB remain enigmatic. We hypothese that the mechanisms of the TRN-VB pathway underlay frequency-selective control of ventrobasal thalamus by GABAergic inhibition of thalamic reticular nucleus in chronic inflammatory pain. In the present study, we will combine in vivo mutichannel recording, whole-cell patch-calmping, behavioral testing and optogenetics to characterize the TRN-driven thalamocortical networks responsible for pain behaviors in rats or mice with complete Freund’s adjuvant induced chronic inflammatory pain. We will investigate the electrophysiology dynamics of thalamocortical network, animal behaviors and the possible mechanism of synaptic and extra-synaptic GABA A receptors with optogenetic activation of TRN-VB pathway at 10 and 100 Hz frequencies. This study will provide new ideas and targets for clinical treatment of chronic pain.

腹侧基底丘脑(Ventrobasal thalamus, VB)是痛觉形成重要的环节，其抑制性信号主要来源于丘脑网状核(thalamic reticular nucleus,TRN)的GABA能抑制。TRN被认为是VB到皮层信息传递过程中重要的调控核团。我们前期研究发现TRN到VB的GABA能信号减低参与慢性炎症痛。但TRN-VB的GABA信号参与慢性炎症痛的电生理学及神经网络层面的调控机制，至今仍不明确。本课题以完全弗氏佐剂诱导的慢性炎症痛为模型，结合在脑片膜片钳，动物行为学及光遗传学等技术，研究TRN-VB高频率(100 Hz)和低频率(10 Hz)电活动对VB、皮层及行为学的不同影响，其具体机制是否是作用突触内、外GABA A型受体，诱导VB谷氨酸能神经元放电模式转化；旨在阐明TRN-VB的GABA能抑制通过频率依赖性的调控VB放电模式，参与慢性炎症痛,为临床治疗慢性痛提供新靶点。

腹侧基底丘脑(Ventrobasal thalamus, VB)是痛觉形成重要的环节，其抑制性信号主要来源于丘脑网状核(thalamic reticular nucleus,TRN)的GABA能抑制。TRN被认为是VB到皮层信息传递过程中重要的调控核团。我们的研究发现TRN到VB的GABA能信号减低参与慢性炎症痛。本项目对TRN-VB的GABA信号参与慢性炎症痛的电生理学及神经网络层面的调控机制进一步深入探索。本课题以完全弗氏佐剂诱导的慢性炎症痛为模型，结合在脑片膜片钳，动物行为学及光遗传学等技术，研究TRN-VB高频率(100 Hz)和低频率(10 Hz)电活动对VB及行为学的不同影响，其具体机制是作用突触内、外GABA A型受体，诱导VB谷氨酸能神经元放电模式转化；阐明了TRN-VB的GABA能抑制通过频率依赖性的调控VB放电模式，参与慢性炎症痛，为临床治疗慢性痛提供新靶点。