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

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.