权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Restoring cognition by optogenetically rescuing gamma rhythms in PFC interneurons

通过光遗传学拯救 PFC 中间神经元的伽马节律来恢复认知

基本信息

批准号：
8860969
负责人：
Vikaas Singh Sohal
金额：
$ 38.83万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-03-01 至 2020-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8860969
关键词：
Acute Adolescent Adult Affect Appearance Attention Auditory Autistic Disorder Behavioral Brain Calcium-Binding Proteins Cognition Cognitive Cognitive deficits Cognitive remediation Cues Defect Development Disease Distress Dominant-Negative Mutation Electroencephalography Event-Related Potentials FMR1 Family Food Frequencies Functional disorder Goals Hippocampus (Brain)Interneuron function Interneurons Laboratories Learning Life Light Link Measures Modeling Mus Mutant Strains Mice Odors Parvalbumins Patients Performance Play Population Prefrontal Cortex Process Property Proteins Refractory Rewards Role Schizophrenia Short-Term Memory Stimulus Structure Testing Variant Visual auditory stimulus base calmodulin-dependent protein kinase II cognitive process disability excitatory neuron flexibility follow-up improved neuropsychiatry optogenetics public health relevance restoration transcription factor

项目摘要

DESCRIPTION (provided by applicant): Synchronized, rhythmic activity within the prefrontal cortex (PFC) and at frequencies in the gamma range (~30- 120 Hz) is believed to contribute to many cognitive processes. A specific class of GABAergic interneurons (FSINs) that can be identified based either on their fast-spiking properties, or based on their expression of the calcium-binding protein parvalbumin (PV), play a critical role in these oscillations. Both prefrontal FSINs and gamma oscillations are abnormal in schizophrenia, suggesting that gamma oscillations may represent an important link between interneuron dysfunction and cognitive deficits; similar mechanisms may contribute to other neuropsychiatric disorders such as autism. Here, we will build on a recent study from our laboratory which found that stimulating interneurons at gamma frequencies can produce long-lasting improvements in cognitive flexibility in mice. Specifically, we studied mutant mice which model abnormalities in FSINs and gamma oscillations, as well as deficits in cognitive flexibility that are associated with schizophrenia. We found that using light sensitive proteins to active interneurons in the PFC at gamma frequencies enables these mice to perform normally on a task that measures cognitive flexibility. By contrast, activating these interneurons at other frequencies was ineffective. Now, we propose to explore whether activating PFC interneurons at gamma frequencies can enhance cognition in other contexts. For example, we will test whether activating PFC interneurons at gamma frequencies can rescue cognitive deficits in other mutant mice, in which interneuron function is not the sole or primary defect, or can produce supra-normal levels of performance in normal mice. We will also explore whether activating PFC interneurons at gamma frequencies can improve performance in tasks that measure other aspects of cognition, e.g. working memory. A second direction will be testing the idea that activating PFC interneurons at gamma-frequencies might enhance cognition by facilitating interactions between the PFC and other brain structures. In order to test this idea, we will measure how stimulating interneurons affects the degree to which activity in the PFC is synchronized with other structures. We will also determine whether activating PFC interneurons at gamma frequencies alters activity in other brain structures that are involved in cognitive flexibility. The long-term goal of this project is o determine whether enhancing interneuron-driven gamma oscillations in the PFC can improve cognitive deficits associated with schizophrenia and related disorders, and to identify possible mechanisms through which this might occur.