MRC funded PhD student,
Neural disinhibition, i.e. reduced inhibitory GABA transmission, has been implicated in important neuropsychiatric disorders. Cortico-hippocampal disinhibition has been implicated in cognitive… read more
Neural disinhibition, i.e. reduced inhibitory GABA transmission, has been implicated in important neuropsychiatric disorders. Cortico-hippocampal disinhibition has been implicated in cognitive disorders, including schizophrenia and age-related cognitive decline. Striatal disinhibition has been implicated in Tourette syndrome. To study brain-wide functional changes caused by cortico-hippocampo-striatal neural disinhibition, we use translational neuroimaging methods in rat models of regional neural disinhibition. Magnetic resonance spectroscopy (MRS) is used to measure neurotransmitters (GABA, glutamate) and neurometabolites and high-resolution single-photon-emission-computerised tomography (SPECT) to measure regional cerebral blood flow (rCBF). The rat models involve intra-cerebral microinfusion of GABA receptor antagonists, to characterise neuro-behavioural/cognitive effects of neural disinhibition. We test the hypothesis that regional neural disinhibition causes changes in the disinhibited region and in projection sites (e.g., prefrontal cortex for hippocampal disinhibition, motor cortex for striatal disinhibition), which will be reflected by rCBF and MRS changes. Our findings will reveal potential biomarkers of neuropsychiatric disorders associated with neural disinhibition and brain mechanisms relevant to symptom generation in these disorders. The project involves international collaboration with partners in Israel and Germany and a research placement in Germany. This project is an MRC studentship.