Understanding the basic biology of the brain - how it develops and how it functions - remains one of the greatest challenges in science. Our work focuses largely on a group of nerve cells called inhibitory interneurons, the primary source of inhibition in the brain of most animals. We have discovered some of the ways in which disease-linked genes regulate the development and function of these cells and are beginning to learn how they operate at the circuit and behavioral level as well as in disorders of brain development such as epilepsy, intellectual disability and/or autism. To do this, we analyze mice with mutations in genes linked to epilepsy and, more recently, induced pluripotent stem cells (iPSCs) derived from the skin of human patients.

The lab is also designing circuit-based therapies to rewire different brain structures in living animals and reprogram their behavior. Historically, modern medicine has relied on pharmacological approaches to deliver drugs throughout the body. While these chronic drug strategies can work, they are quite crude and often result in unwanted side effects. By focusing on a circuit-level understanding of how the brain generates behavior, we recently discovered a way to stop seizures (and other behavioral problems) in severely epileptic mice. This approach involves grafting new inhibitory interneurons into areas of the brain important for seizure generation. Based on this work, we have an increasing interest in the generation of specific, well-defined cell types for use in cell therapy and continue to explore new avenues for rewiring the nervous system.

Neural circuits, synapses, stem cells, epilepsy, autism, hippocampal plasticity, electrophysiology