A link between NMDA receptor function and GABAergic inhibition in the modulation of cognition?

本项目将探讨NMDA受体功能与海马和前额叶GABA抑制在认知调节中的联系。学生将主要在NMDA受体功能减退（注射NMDA受体拮抗剂苯环己哌啶）和海马和前额GABA功能降低的大鼠模型中结合联合收割机神经生物学和行为学方法，即所谓的神经去抑制（脑内注入GABA拮抗剂印防己毒素）。她还将研究母体免疫激活模型中的NMDA和GABA标记物，该模型显示成年后代的认知缺陷可能与GABA和GABA能变化有关，并且正在由行业合作伙伴开发。NMDA受体功能减退和神经去抑制都与认知障碍有关，包括精神分裂症和与年龄相关的认知下降，和NMDA受体功能减退模型广泛用于药物发现。海马和前额叶GABA抑制是认知功能所必需的，如注意力和记忆力。NMDA受体是维持GABA抑制所必需的，啮齿动物中的NMDA受体功能减退减少海马和前额GABA标记物。该项目的实验将检验NMDA受体功能减退通过引起海马和前额神经抑制解除而损害认知的总体假设，该项目涉及支持整个生命过程健康的基础生物科学的战略优先事项，提供研究神经行为机制的培训，这些机制是整个生命周期健康认知和行为的基础。更具体地说，该项目将解决2015年MRC和BBSRC脆弱技能和能力审查中强调的两个重要的生物科学技能差距：-大鼠模型的体内神经生物学和认知/行为研究培训，解决体内综合技能的短缺。- 在统计和行为和电生理数据集的分析培训，解决生物科学的统计和计算技能的差距，以及数据驱动的生物学的战略优先事项。行业合作伙伴，合同研究组织b-neuro，位于曼彻斯特大学，在蓬勃发展的学术环境中运作，为制药公司，NHS和学术界培养博士和硕士学生。因此，b-neuro提供学术环境和相关培训计划的所有好处，结合为合同研究组织工作以及与定期访问b-neuro的制药行业研究科学家互动所带来的独特经验和培训。

This project will address the link between NMDA receptor function and hippocampal and prefrontal GABA inhibition in the modulation of cognition. The student will mainly combine neurobiological and behavioural methods in rat models of NMDA receptor hypofunction (injection of NMDA receptor antagonist phencyclidine) and of reduced hippocampal and prefrontal GABA function, so-called neural disinhibition (intracerebral infusion of GABA antagonist picrotoxin). She will also examine NMDA and GABA markers in the maternal immune activation model, which shows cognitive deficits in the adult offspring that may be linked to GABA and glutamatergic changes and is under development by the industry partner.Both NMDA receptor hypofunction and neural disinhibition have been implicated in cognitive disorders, including schizophrenia and age-related cognitive decline, and NMDA receptor hypofunction models are widely used in drug discovery. Hippocampal and prefrontal GABA inhibition is required for cognitive functions, such as attention and memory. NMDA receptors are required to maintain GABA inhibition, with NMDA receptor hypofunction in rodents reducing hippocampal and prefrontal GABA markers. The experiments in this project will examine the overarching hypothesis that NMDA receptor hypofunction impairs cognition by causing hippocampal and prefrontal neural disinhibition.The project addresses the strategic priority of basic bioscience underpinning health across the lifecourse, providing training in the study of neuro-behavioural mechanisms that underlie healthy cognition and behaviour across the life span. More specifically, the project will address two important bioscience skill gaps highlighted in the 2015 MRC and BBSRC Review of Vulnerable skills and capabilities:- training in the in vivo neurobiological and cognitive/behavioural study of rat models, addressing the shortage of integrative in vivo skills. - training in statistics and the analysis of behavioural and electrophysiological data sets, addressing the statistical and computational skills gap in the Biosciences, as well as the strategic priority of data-driven biology.The industry partner, the contract research organization b-neuro, is situated with the University of Manchester, operating within a thriving academic environment and training PhD and MSc students for pharmaceutical companies, NHS and academia. Therefore, b-neuro offers all the benefits of an academic environment and associated training programmes, combined with the unique experience and training that comes with working for a contract research organization and from interactions with research scientists from the Pharmaceutical Industry who visit b-neuro on a regular basis.