Translational neuroimaging studies in rat models of regional neural disinhibition

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Neural disinhibition, i.e. reduced inhibitory GABA transmission, has been implicated in important neuropsychiatric disorders. More specifically, cortico-hippocampal disinhibition has been implicated in cognitive disorders, including schizophrenia and age-related cognitive decline, whereas striatal disinhibition has been implicated in Tourette syndrome.To study brain-wide functional changes caused by cortico-hippocampo-striatal neural disinhibition, the student will use translational neuroimaging methods in rat models of regional neural disinhibition. She will use magnetic resonance spectroscopy (MRS) 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 and have previously been used by us and our collaborators to characterise neuro-behavioural/cognitive effects of neural disinhibition. We will 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.The project addresses the following MRC skill priorities:- interdisciplinary training (at the imaging physics-neuroscience, clinical-animal model interfaces) in integrative in vivo skills in rat models; - development of quantitative skills required for the statistical analysis of the data generated.