Optical probing of neural networks in the developing neocortex
The brain represents one of the most complex biological systems known to man. It is fundamental to processes such as learning, memory and language. Central to these actions are an array of cells whose diversity has proven to be an obstacle to our understanding of brain function and conversely dysfunction. At present we define two categories of nerve cell in the forebrain: excitatory pyramidal cells, and local inhibitory nerve cells termed interneurons. The latter, which represent only a minor component of the total number of cells in the brain, are critical to normal function.
Research in the group is focused on using the power of developmental genetics to interrogate the contribution of interneurons to emergent brain activity. The purpose being to gain an understanding of the simple, early brain that will establish a set of rules for the more complex mature brain and provide the foundation for a better understanding of interneuron-related neurological conditions. Such an approach has proven hard to pursue in the past due to the dynamic nature of the developing brain and the difficulty in targeting specific cells. To overcome this, we aim to take advantage of genes crucial for cell identity. Our recent findings have revealed that the fate of a cell is specified early on in the embryo in response to a genetic code, which acts through a cascade of checkpoints to generate the diversity present in the adult. We have begun to crack this code and are now able to pinpoint where and when interneuron are born. Unfortunately the story is still largely incomplete and there are no genes specific to any one class of interneuron. The benefits of resolving this code would be immense as researchers will be able to unequivocally identify the same cells time and time again and target their research more effectively. Furthermore this approach enables less invasive techniques to be applied that more traditional physiological approaches that might give researchers a different, perhaps more realistic, perspective on brain function.
Our lab is focused on answering how genetics and physiology intertwine to build a structure as exquisite as the mammalian brain. We are intrigued as to how these forces sculpt the normal, emergent circuitry of the neocortex, and how on occasion deficits in this highly regulated process bring about a range of psychiatric disorders.
The lab employs a wide range of genetic technologies in conjunction with classical electrophysiology and laser scanning photostimulation (LSPS) to address our principle research objectives. Current areas of research include:
1. Novel genetic determinants of cortical interneuron diversity
2. Development of high resolution single-photon LSPS as a tool to map developing cortical circuits
3. Application of new generation Channel Rhodopsins: faster, stronger, better?
We are dedicated to working in a small collaborative team that has a true passion for understanding the developing brain at all levels. If this is of interest then feel free to contact Simon Butt to discuss possible graduate studentships, shared research interests or future collaborations.
Daniel Lyngholm (Post-doc) > Strathclyde Institute Of Pharmacy And Biomedical Sciences
Sofia Deleniv (Neuroscience MSc student)
André Marques-Smith (DPhil student) > Department of Developmental Neurobiology, KCL
Anne Hedegaard (Neuroscience MSc student)
Tom Lickiss (Post-doc) > The Institute for Reconstructive Neurobiology, Bonn
Paul Anastasiades (PhD student) > The Center for Neural Science, NYU
Anna-Kristin Kaufmann (Neuroscience MSc student)
James Cooke (Neuroscience MSc student)