Formation of the earliest circuits in the cerebral cortex

点击翻译按钮获取中文摘要

Building the brain is like erecting a huge building. The construction requires a dynamic scaffold which is built and modified along with the final permanent structure. During and after the completion of the building, the scaffold has to be dismantled at the right places and at the right time. The subplate, formed by the earliest generated and largely transient cortical neurons, is the developmental scaffold of the cortex of the brain, and disruption of these cells may be the source of many developmental disorders and therefore a fundamental topic to study. Developmental disorders of the cerebral cortical (schizophrenia, autism, attention deficit/hyperactivity disorder, ADHD) and hypoxic injuries around the time of birth (periventricular leucomalacia, PVL) involve cells of the subplate. The Molnar group has been investigating the integration of subplate cells into the intracortical and extracortical circuitry, their neurochemical properties and physiological characteristics over the last 16 years. Just like the building scaffold has to change dynamically during the course of the construction, so does the structure and circuitry formed by subplate cells during development. We aim to characterize gene expression patterns in the subplate throughout the life of a mouse and optimize some of these markers for use on human tissue. For subgroups of subplate cells identified by these markers, we aim to characterize their structure and projection pattern and how they function as part of the complex circuitry that is the mouse brain. These approaches require much specialised skills, which are beyond the scope of a single research group. The proposed collaboration will foster the interactions between a physiology laboratory (Dr Ole Paulsen) and a cellular/molecular and anatomical group and will open opportunities for the initiation of clinical applications in neuro-imaging, psychiatry, and neuropathology.