Deep posteromedial cortical rhythm in dissociation.
Deep posteromedial cortical rhythm in dissociation.
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DOI：
10.1038/s41586-020-2731-9
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发表时间：
2020-10
期刊：
影响因子：
64.8
通讯作者：
Deisseroth K
中科院分区：
文献类型：
--
作者：
Vesuna S;Kauvar IV;Richman E;Gore F;Oskotsky T;Sava-Segal C;Luo L;Malenka RC;Henderson JM;Nuyujukian P;Parvizi J;Deisseroth K
先进的成像方法现在允许细胞类型特异性记录哺乳动物大脑中的神经活动，这可能有助于探索全脑动力学模式如何产生复杂的行为状态。分离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，包括刺激检测与刺激相关的情感反应的分离。解离可由于创伤、癫痫或解离性药物使用而发生，但尽管其具有实质性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。在此，我们通过精确剂量的氯胺酮或苯环己哌啶给药，在小鼠中建立了这种解离样状态。神经活动的大范围成像显示，这些解离剂在压后皮质的第5层神经元中引起1-3 Hz的节律。四个同时部署的高密度探针的电生理记录显示，压后皮质与丘脑回路解剖学上连接的组件的节律耦合，但与大多数其他大脑区域的解耦是无效的，包括一个显着的负相关性与丘脑前突核。在测试因果关系的意义，我们发现，有节奏的光遗传激活后压皮层第5层神经元重演解离样行为的影响。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（HCN 1）起搏器来诱导这种节律并引起解离样行为效应。在一位局灶性癫痫患者中，来自整个大脑的同步颅内立体脑电描记术记录显示，同源深后内侧皮质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，并且该区域的局部短暂电刺激引起解离体验。这些结果确定了保守的深层后内侧皮质节律的分子，细胞和生理特性的分离状态的基础。
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. 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, 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.