美国斯坦福大学Karl Deisseroth研究团队揭示神经分裂背后的神经节律。该项研究成果于2020年9月16日在线发表在《自然》杂志上。

通过精确剂量的氯胺酮或苯环利定诱导，研究人员在小鼠中建立了分裂样状态。神经活动的大规模成像显示，这些分裂剂在压后皮质的第5层神经元中引起1-3 Hz的节律。用四个同时部署的高密度探针进行的电生理记录显示，压后皮质与丘脑回路解剖学连接成分的节律性耦合，但观察到与大多数其他大脑区域的解耦，包括与额叶丘脑核的显著负相关。

在检验因果关系的意义上，研究人员发现压后皮质第5层神经元的节奏性光遗传学激活可以概括分裂样的行为效应。全身性氯胺酮需要局部脾后HCN1（hyperpolarization-activated cyclic-nucleotide-gated potassium channel 1）起搏器来诱导这种节律并引起类似分裂的行为效应。

在患有局灶性癫痫的患者中，同时通过颅内立体脑电图记录发现，在同源的深后内侧皮质中有类似的局部节律，这在时间上与癫痫发作前的自我报告的分裂有关，而对该区域的局部短暂电刺激会引起分裂的经历。

这些结果确定了保守的深内膜后皮质节律的分子、细胞和生理学性质，这是分裂状态的基础。

现在，先进的成像方法可以在哺乳动物的大脑中记录特定于细胞类型的神经活动，从而有可能探索全脑动态模式如何引起复杂的行为状态。分裂是一种改变的行为状态，其中经验的完整性被破坏，导致可再现的认知现象。分裂可能是由于外伤、癫痫或分裂药物的使用引起的，但是尽管其具有重要的基础和临床意义，但这种状态的潜在神经生理学尚不清楚。

附：英文原文

Title: Deep posteromedial cortical rhythm in dissociation

Author: Sam Vesuna, Isaac V. Kauvar, Ethan Richman, Felicity Gore, Tomiko Oskotsky, Clara Sava-Segal, Liqun Luo, Robert C. Malenka, Jaimie M. Henderson, Paul Nuyujukian, Josef Parvizi, Karl Deisseroth

Issue&Volume: 2020-09-16

Abstract: Advanced imaging methods now allow cell-type-specific recording of neural activity across the mammalian brain, potentially enabling the exploration of how brain-wide dynamical patterns give rise to complex behavioural states1,2,3,4,5,6,7,8,9,10,11,12. Dissociation is an altered behavioural state in which the integrity of experience is disrupted, resulting in reproducible cognitive phenomena including the dissociation of stimulus detection from stimulus-related affective responses. Dissociation can occur as a result of trauma, epilepsy or dissociative drug use13,14, but despite its substantial basic and clinical importance, the underlying neurophysiology of this state is unknown. Here we establish such a dissociation-like state in mice, induced by precisely-dosed administration of ketamine or phencyclidine. Large-scale imaging of neural activity revealed that these dissociative agents elicited a 1–3-Hz rhythm in layer 5 neurons of the retrosplenial cortex. Electrophysiological recording with four simultaneously deployed high-density probes revealed rhythmic coupling of the retrosplenial cortex with anatomically connected components of thalamus circuitry, but uncoupling from most other brain regions was observed—including a notable inverse correlation with frontally projecting thalamic nuclei. In testing for causal significance, we found that rhythmic optogenetic activation of retrosplenial cortex layer 5 neurons recapitulated dissociation-like behavioural effects. Local retrosplenial hyperpolarization-activated cyclic-nucleotide-gated potassium channel 1 (HCN1) pacemakers were required for systemic ketamine to induce this rhythm and to elicit dissociation-like behavioural effects. In a patient with focal epilepsy, simultaneous intracranial stereoencephalography recordings from across the brain revealed a similarly localized rhythm in the homologous deep posteromedial cortex that was temporally correlated with pre-seizure self-reported dissociation, and local brief electrical stimulation of this region elicited dissociative experiences. These results identify the molecular, cellular and physiological properties of a conserved deep posteromedial cortical rhythm that underlies states of dissociation.

DOI: 10.1038/s41586-020-2731-9

Source: https://www.nature.com/articles/s41586-020-2731-9