Mitchell Chesler

Mitchell Chesler, MD, PhD

Professor, Department of Neurosurgery

Professor, Department of Neuroscience and Physiology

Keywords
channels and transporters, molecular, cellular, & translational neuroscience, regulation and modulation of pH in the nervous system, neuronal and glial injury
Summary

Changes in pH mediate physiological signaling in a wide variety of cell types. Often, these pH shifts occur in minutes to hours, when growth factor or classical hormone receptors are coupled to the activation of membrane acid transporters. In the nervous system, however, electrical signaling occurs in milliseconds to seconds. Recently, we have discovered mechanisms that can modulate pH on a similarly rapid time scale. In the brain, the pH shifts associated with electrical activity are regionally specific and undergo developmental changes.

The goal of my research is to elucidate the mechanisms responsible for rapid acid transport during neuronal activity, to establish how the resulting pH changes are regulated, and to determine how these pH shifts influence normal and pathological brain function.

We have established that neural activity triggers a rapid loss of acid from the extracellular space. This is particularly evident in the hippocampus, where extracellular pH can rise within a few milliseconds of synaptic transmission. Since excitatory postsynaptic NMDA receptors and voltage-dependent calcium channels are sensitive to external acid, we are exploring how these pH shifts modify neuronal excitability and synaptic transmission.

Our recent work has established that neurons generate a rise in extracellular pH near the synapse, thereby boosting excitatory synaptic transmission through its effect on NMDA receptors. These findings have translational relevance for seizure, stroke, traumatic brain injury, and migraine; these pathologies intimately involve NMDA receptors and have been associated with extremely large extracellular pH changes in experimental models.

Phone

212-263-6318

Academic office

455 First Avenue

Eighth Floor, Room 875

New York, NY 10016

Lab Website
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Professor, Department of Neurosurgery

Professor, Department of Neuroscience and Physiology

Associate Director, Medical Science Training Program

MD from New York University

PhD from New York University

Fellowship, Cornell U. Medical College, Neurology

Fellowship, Brigham and Women's Hospital Harvard Medical School, Pathology

Chen, Huei-Ying; Chesler, Mitchell

Journal of neuroscience. 2015 Jan 21; 35(3):873-877

Makani, Sachin; Chen, Huei-Ying; Esquenazi, Susana; Shah, Gul N; Waheed, Abdul; Sly, William S; Chesler, Mitchell

Journal of neuroscience. 2012 Nov 21; 32(47):16754-16762

Svichar, Nataliya; Esquenazi, Susana; Chen, Huei-Ying; Chesler, Mitchell

Journal of neuroscience. 2011 May 11; 31(19):6997-7004

Makani, Sachin; Chesler, Mitchell

Journal of neurophysiology. 2010 Feb; 103(2):667-676

Makani, Sachin; Chesler, Mitchell

Journal of neuroscience. 2007 Jul 11; 27(28):7438-7446

Fedirko, Nataliya; Svichar, Nataliya; Chesler, Mitchell

Journal of neurophysiology. 2006 Aug; 96(2):919-924

Tong, Chi-Kun; Chen, Kevin; Chesler, Mitchell

Journal of neurophysiology. 2006 Jun; 95(6):3686-3697

Chesler, Mitchell

Physiological reviews. 2003 Oct; 83(4):1183-1221