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

Physiological signaling mediated by changes in pH (acid-base balance) has been documented in a wide variety of cell types. Often, growth factor or classical hormone receptors are coupled to the activation of membrane acid transporters, resulting in pH shifts over minutes to hours. In the nervous system, by contrast, electrical signaling occurs in milliseconds to seconds. Recently, mechanisms have been discovered which 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 focus of my laboratory is to elucidate the mechanisms which rapidly transport acid 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 synaptic transmission can give rise to an increase in extracellular pH within a few milliseconds. Since excitatory post-synaptic NMDA receptors, and voltage-dependent calcium channels are sensitive to external acid, we are particularly interested in how these pH shifts modify neuronal excitability and synaptic transmission. Recent work has established that neurons generate a rise in extracellular pH near the synapse, which serves to boost excitatory synaptic transmission through its effect on NMDA receptors. These findings have translational relevance for seizure, stroke, traumatic brain injury, and migraine, as 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