Using new methods for voltage imaging to assay the engagement of specific cell-types and brain rhythms in prefrontal-dependent cognition.

使用电压成像的新方法来分析特定细胞类型和大脑节律在前额叶依赖性认知中的参与情况。

• 批准号: 10413947
• 负责人: Vikaas Singh Sohal
• 金额: $ 40.38万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-05 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10413947
• 关键词: Address; Affect; Amphetamines; Anti-Cholinergics; Antipsychotic Agents; Area; Behavioral; Biological Assay; Biological Markers; Biological Process; Bipolar Disorder; Brain; Brain region; Clonazepam; Cognition; Cognitive; Cognitive deficits; Communication; Delusions; Development; Disease; Electroencephalography; Evaluation; Frequencies; Functional disorder; Hallucinations; Heart; Human; Image; Impairment; Individual; Interneuron function; Interneurons; Link; Location; Measures; Methods; Modeling; Mus; Mutant Strains Mice; Parvalbumins; Pattern; Performance; Pharmaceutical Preparations; Pharmacology; Play; Population; Prefrontal Cortex; Process; Refractory; Rodent; Schizophrenia; Signal Transduction; Site; Somatostatin; Symptoms; Testing; Therapeutic; Translating; Work; base; cell type; clinically relevant; cognitive task; disability; economic cost; executive function; experimental study; flexibility; neurophysiology; novel; novel therapeutics; optogenetics; public health relevance; recruit; voltage

PROJECT SUMMARY Cognitive deficits represent the major cause of disability in schizophrenia but are refractory to all existing treatments. EEG oscillations in the gamma-frequency range are recruited by many cognitive tasks, and task- evoked gamma oscillations are deficient in schizophrenia. Furthermore, gamma oscillations are generated by parvalbumin interneurons, which are abnormal in schizophrenia. This suggests that gamma oscillations may be biomarkers for cognitive deficits and parvalbumin interneuron dysfunction in schizophrenia. In fact, many studies suggest that gamma oscillations may actively contribute to cortical circuit functions that are necessary for cognition. Indeed, our previous work has shown that optogenetically restoring interneuron-generated gamma oscillations in the prefrontal cortex can rescue cognitive deficits in mutant mice. However, there are many ways to measure gamma oscillations – some of these capture the strength of gamma oscillations at a single site whereas others reflect synchronization across sites. Our recent work suggests that long-range synchronization of gamma-frequency activity in PV interneurons, rather than just gamma-frequency activity at a single site, may be required for prefrontal cortex-dependent cognitive flexibility. Furthermore, we have developed new ways of measuring signals from genetically encoded voltage indicators in order to measure gamma-frequency synchronization between specific cell-types at different locations. We will now leverage these advances to: (1) use our novel analyses and GEVIs to directly measure cell-type specific gamma- frequency synchronization in behaving rodents; (2) determine which particular ways of quantifying EEG gamma oscillations best capture this synchronization; (3) evaluate how well these EEG measures correlate with changes in PV interneuron synchronization and behavioral performance elicited by several pharmacological manipulations including some which are known to rescue deficits in gamma oscillations and prefrontal-dependent cognition in mutant mice, and (4) validate, via optogenetics, that these EEG measures are sensitive and specific indicators for changes in PV interneuron function. This project will define particular EEG measures that reflect cell-type specific patterns of long-range synchronization underlying specific aspects of cognition.

项目总结

项目成果

Transforming Discoveries About Cortical Microcircuits and Gamma Oscillations Into New Treatments for Cognitive Deficits in Schizophrenia.

将皮质微电路和伽马振荡的发现转化为精神分裂症认知缺陷的新疗法。

• DOI: 10.1176/appi.ajp.20220147
• 发表时间: 2022
• 期刊: The American journal of psychiatry
• 作者: Sohal,VikaasS

Long-range inhibition synchronizes and updates prefrontal task activity.

远程抑制同步和更新前额叶任务活动。

• DOI: 10.1038/s41586-023-06012-9
• 发表时间: 2023-05
• 期刊: NATURE
• 影响因子: 64.8
• 作者: Cho, Kathleen K. A.;Shi, Jingcheng;Phensy, Aarron J.;Turner, Marc L.;Sohal, Vikaas S.
• 通讯作者: Sohal, Vikaas S.