Research in the Chesler Laboratory

How is brain pH regulated?

Do changes in pH caused by neural activity modulate brain function normally, or in pathological settings?

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Research in Dr. Chesler’s laboratory focuses on mechanisms that both regulate and modulate pH in the mammalian brain, and the role of these processes in pathological settings such as seizure, stroke, cardiac arrest, and the proliferation of brain tumors. These studies strive to understand how intracellular and extracellular pH serve as modulators of normal and abnormal brain function. Studies focus on the identification and understanding of the enzymes and transport proteins responsible for modulation and regulation of brain pH. The laboratory employs a variety of recording techniques that include patch clamp electrophysiology, fluorescence imaging, and ion-selective microelectrodes. These methods are used in concert with standard molecular biological approaches to study cultured cells, or brain slices from mice with gene deletions or knock downs of specific transporters or enzymes. Experiments have shown that rapid increases in extracellular pH accompany evoked synchronous neural firing, seizure, and cortical spreading depression. These changes are linked to calcium entry into neurons, and have a strong influence on NMDA receptors. Additional studies target the mechanisms of intracellular pH regulation in neurons and glial cells. The transport systems responsible for the control of cytosolic pH can have deleterious effects under pathological conditions, contributing to edema as well as necrotic and apoptotic dell death. Understanding the pathophysiological impact of these processes may lead to rational strategies for the treatment and management of brain injury.

Left: pH and patch clamp microelectrodes for recording changes in neuronal surface pH elicited by neural activity.

Right: Addition of carbonic anhydrase to brain slice media enhances buffering near excitatory synapses and markedly suppresses neural activity elicited by excitatory synaptic transmission.