Translational neuroimaging studies in rat models of regional neural disinhibition

神经去抑制，即抑制性GABA传递减少，与重要的神经精神障碍有关。更具体地说，皮质-海马去抑制与认知障碍有关，包括精神分裂症和与年龄相关的认知衰退，而纹状体去抑制与Tourette综合征有关。为了研究皮质-海马-纹状体神经去抑制引起的全脑功能变化，学生将在大鼠局部神经去抑制模型中使用翻译神经成像方法。她将使用磁共振波谱（MRS）测量神经递质（GABA、谷氨酸）和神经代谢物，并使用高分辨率单光子发射计算机断层扫描（SPECT）测量局部脑血流量（rCBF）。大鼠模型涉及GABA受体拮抗剂的脑内微量输注，并且先前已被我们和我们的合作者用于研究神经去抑制的神经行为/认知效应。我们将检验区域神经去抑制引起去抑制区域和投射部位变化的假设（例如，前额叶皮层用于海马去抑制，运动皮层用于纹状体去抑制），这将通过rCBF和MRS变化来反映。我们的研究结果将揭示与神经去抑制相关的神经精神疾病的潜在生物标志物以及与这些疾病中症状产生相关的大脑机制。该项目涉及与以色列和德国的合作伙伴以及德国的研究安排的国际合作。该项目解决了以下MRC技能优先事项：-跨学科培训（在成像物理学-神经科学，临床-动物模型接口）在大鼠模型的综合体内技能;- 发展对所产生的数据进行统计分析所需的定量技能。

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.