John Welsh, Ph.D.
Professor

Email: john.welsh2@drexelmed.edu

Functional significance of neuronal oscillation

It has been known since the first electrophysiological recordings that the brain is an intrinsically rhythmic system. Nevertheless, the functional significance of brain rhythm remains an intensely debated and, hence, investigated area of neuroscience. As alterations in brain rhythms underlie many, if not all, neuropsychiatric and motor disorders, the genetic and physiological bases of brain rhythm provide a compelling handle toward developing new classes of therapeutic drugs. We are examining the role of altered brain rhythm and coherence in animal models of neuropsychiatric and movement disorders.

Our recent work on fast cerebral rhythms is providing a basis for understanding the pathophysiology of the language impairments in autism. This work is done in a bidirectional research program linking our basic science laboratory with the clinical electrophysiological laboratory of Dr. Timothy Roberts at Children’s Hospital of Pennsylvania. Our goal in creating a bidirectional research program is to allow findings from the clinical electrophysiology laboratory to inform mechanistic studies in animal models and, thereafter, to allow the latter to guide novel therapeutic strategies that can be related back to the clinic. Our work on cerebellar rhythms is uncovering the functional basis of electrical coupling in the brain and its possible dysfunction leading to dystonia and essential tremor, the most common motor neurological disorder.

Our experiments are inherently multidisciplinary and involve behavioral conditioning, in vivo multiple microelectrode neurophysiology, gene transfer using viral-based vectors, and real-time optical imaging of neuronal circuits.

Organization of inferior olive dendritic arbors (red) in an electrically uncoupled network (GFP, green) produced by lentiviral knockdown of connexin36, a neuronal gap junction protein. (see Placantonakis et al., 2006).

Recent pubications

Welsh, J. P., Yuen, G., Placantonakis, D. G., Vu, T., Haiss, F., O’Hearn, E., Molliver, M. E., and Aicher, S. A. (2002). Why do Purkinje cells die so easily after global brain ischemia? Aldolase C, EAAT4 and the cerebellar contribution to post-hypoxic myoclonus. Advances in Neurology, Myoclonus and Paroxysmal Dyskinesias, 89: 331-359.

Welsh, J. P. (2002). Functional significance of climbing fiber synchrony: A population coding and behavioral analysis. Annals of the New York Academy of Sciences, The Cerebellum: Recent Developments in Cerebellar Research 978: 188-204.

Johnson, J. L., and Welsh, J. P. (2003). Independently-moveable multielectrode array to record multiple fast-spiking neurons in the cerebral cortex during cognition. Methods 30: 64-78.

Placantonakis, D. G., Bukovsky, A. A., Zeng, X-H., Kiem, H. P., and Welsh, J. P. (2004). Fundamental role of inferior olive connexin 36 in muscle coherence during tremor. Proceedings of the National Academy of Sciences, U.S.A. 101: 7164-7169.

Welsh, J. P., Ahn, E. S., and Placantonakis, D. G. (2005). Is autism due to brain desynchronization? International Journal for Developmental Neuroscience. Special Issue on Autism: Modeling Human Brain Abnormalities in Developing Animal Systems 23: 253-263.

Welsh, J. P., Yamaguchi, H., Zeng X. –H, Kojo M.,. Nakada Y., Takagi A. Sugimori, M., and Llinás R. R. (2005). Normal motor learning during acute blockade of Purkinje cell LTD. Proceedings of the National Academy of Sciences, U.S.A. 102: 17166-17171.

Placantonakis, D. G., Bukovsky, A. A., Aicher, S. A., Kiem, H. P., and Welsh, J. P. (2006). Continuous electrical oscillations emerge from a coupled network: A study of the inferior olive using lentiviral knockdown of connexin36. Journal of Neuroscience 10: 5008-5016.