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 states 1 – 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 use 13 , 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. Dissociative states in mouse and human brains are traced to low-frequency rhythmic neural activity—with distinct molecular, cellular and physiological properties—in the deep retrosplenial cortex and the posteromedial cortex.

中文翻译：

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解离中的深层后内侧皮质节律


先进的成像方法现在可以对哺乳动物大脑中的神经活动进行细胞类型特异性记录，从而有可能探索全脑动态模式如何产生复杂的行为状态 1 – 12 。分离是一种改变的行为状态，其中体验的完整性被破坏，导致可重复的认知现象，包括刺激检测与刺激相关的情感反应的分离。创伤、癫痫或解离性药物使用可能会导致解离 13 、 14 ，但尽管其具有重大的基础和临床重要性，但这种状态的潜在神经生理学尚不清楚。在这里，我们在小鼠中建立了这种类似解离的状态，通过精确剂量的氯胺酮或苯环己哌啶给药来诱导。神经活动的大规模成像显示，这些解离剂在压后皮质第 5 层神经元中引起 1-3 Hz 的节律。使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的解剖学连接组件有节律性耦合，但观察到与大多数其他大脑区域的解耦合，包括与额部突出的丘脑核的显着负相关。在测试因果意义时，我们发现压后皮质第 5 层神经元的节律性光遗传学激活再现了解离样行为效应。全身性氯胺酮需要局部压后超极化激活的环核苷酸门控钾通道 1 (HCN1) 起搏器来诱导这种节律并引发解离样行为效应。 在患有局灶性癫痫的患者中，来自整个大脑的同步颅内立体脑描记术记录显示，在同源的后内侧深层皮层中存在类似的局部节律，该节律与癫痫发作前自我报告的解离在时间上相关，并且对该区域的局部短暂电刺激引发了解离体验。这些结果确定了解离状态下保守的深层后内侧皮质节律的分子、细胞和生理特性。小鼠和人类大脑的解离状态可追溯到深部压后皮层和后内侧皮层的低频节律性神经活动，具有独特的分子、细胞和生理特性。