Park Sanggeon, Cho Jeiwon, Huh Yeowool
Department of Brain and Cognitive Sciences, Scranton College, Ewha Womans University, Seoul 03760, Korea.
Brain Disease Research Institute, Ewha Brain Institute, Ewha Womans University, Seoul 03760, Korea.
Exp Neurobiol. 2023 Dec 31;32(6):387-394. doi: 10.5607/en23018.
Loss of inhibition is suggested to cause pathological pain symptoms. Indeed, some human case reports suggest that lesions including the thalamic reticular nucleus (TRN) which provides major inhibitory inputs to other thalamic nuclei, may induce thalamic pain, a type of neuropathic pain. In support, recent studies demonstrated that activation of GABAergic neurons in the TRN reduces nociceptive responses in mice, reiterating the importance of the TRN in gating nociception. However, whether biochemically distinct neuronal types in the TRN differentially contribute to gating nociception has not been investigated. We, therefore, investigated whether the activity of parvalbumin (PV) and somatostatin (SOM) expressing neurons in the somatosensory TRN differentially modulate nociceptive behaviors using optogenetics and immunostaining techniques. We found that activation of PV neurons in the somatosensory TRN significantly reduced nociceptive behaviors, while activation of SOM neurons in the TRN had no such effect. Also, selective activation of PV neurons, but not SOM neurons, in the TRN activated relatively more PV neurons in the primary somatosensory cortex, which delivers inhibitory effect in the cortex, when measured with cFos and PV double staining. Results of our study suggest that PV neurons in the somatosensory TRN have a stronger influence in regulating nociception and that their activations may provide further inhibition in the somatosensory cortex by activating cortical PV neurons.
抑制作用的丧失被认为会导致病理性疼痛症状。确实,一些人类病例报告表明,包括丘脑网状核(TRN)在内的病变,该核向其他丘脑核提供主要的抑制性输入,可能会诱发丘脑痛,这是一种神经性疼痛。作为支持,最近的研究表明,激活TRN中的GABA能神经元可降低小鼠的伤害性反应,重申了TRN在控制伤害感受中的重要性。然而,TRN中生化特性不同的神经元类型是否对控制伤害感受有不同的作用尚未得到研究。因此,我们使用光遗传学和免疫染色技术研究了体感TRN中表达小白蛋白(PV)和生长抑素(SOM)的神经元的活动是否对伤害性相关行为有不同的调节作用。我们发现,激活体感TRN中的PV神经元可显著降低伤害性相关行为,而激活TRN中的SOM神经元则没有这种作用。此外,当用cFos和PV双重染色测量时,在TRN中选择性激活PV神经元而非SOM神经元,会在初级体感皮层激活相对更多的PV神经元,从而在皮层产生抑制作用。我们的研究结果表明,体感TRN中的PV神经元在调节伤害感受方面有更强的影响,并且它们的激活可能通过激活皮层PV神经元在体感皮层提供进一步的抑制作用。