State Key Laboratory of Organ Failure Research, Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangdong Province Key Laboratory of Psychiatric Disorders, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China.
Transl Psychiatry. 2021 Apr 24;11(1):241. doi: 10.1038/s41398-021-01363-1.
Thalamic reticular nucleus (TRN) is a group of inhibitory neurons surrounding the thalamus. Due to its important role in sensory information processing, TRN is considered as the target nucleus for the pathophysiological investigation of schizophrenia and autism spectrum disorder (ASD). Prepulse inhibition (PPI) of acoustic startle response, a phenomenon that strong stimulus-induced startle reflex is reduced by a weaker prestimulus, is always found impaired in schizophrenia and ASD. But the role of TRN in PPI modulation remains unknown. Here, we report that parvalbumin-expressing (PV+) neurons in TRN are activated by sound stimulation of PPI paradigm. Chemogenetic inhibition of PV+ neurons in TRN impairs PPI performance. Further investigations on the mechanism suggest a model of burst-rebound burst firing in TRN-auditory thalamus (medial geniculate nucleus, MG) circuitry. The burst firing is mediated by T-type calcium channel in TRN, and rebound burst firing needs the participation of GABAB receptor in MG. Overall, these findings support the involvement of TRN in PPI modulation.
丘脑网状核（TRN）是围绕丘脑的一组抑制性神经元。由于其在感觉信息处理中的重要作用，TRN 被认为是精神分裂症和自闭症谱系障碍（ASD）病理生理学研究的目标核。声起始反应的前脉冲抑制（PPI），即强刺激引起的起始反射被较弱的前刺激减弱的现象，在精神分裂症和 ASD 中总是发现受损。但是 TRN 在 PPI 调节中的作用尚不清楚。在这里，我们报告说，TRN 中的表达钙结合蛋白 9（PV+）神经元被 PPI 范式的声音刺激激活。TRN 中 PV+神经元的化学遗传抑制会损害 PPI 表现。对机制的进一步研究表明，TRN-听觉丘脑（内侧膝状体核，MG）回路中存在爆发-反弹爆发式放电的模型。爆发式放电是由 TRN 中的 T 型钙通道介导的，而反弹式爆发式放电需要 MG 中 GABAB 受体的参与。总的来说，这些发现支持 TRN 参与 PPI 调节。
