Jonathan Cohen

Jonathan Cohen, PhD

Bullard Professor of Neurobiology, Emeritus

Ion Channel and Neurotransmitter Biology

Neurons communicate with each other through the release of neurotransmitter molecules such as glutamate, GABA, acetylcholine, dopamine, serotonin, etc. at synapses. When a neurotransmitter binds to its receptor on the membrane of a neuron, it opens up ion channels that result in neuronal excitation or inhibition. Better understanding how this process works has many implications, both for basic neuroscience and our understanding of nervous system disorders.

The Cohen lab focuses on molecular studies of receptors for GABA, the major inhibitory neurotransmitter in the brain, and acetylcholine, an excitatory neurotransmitter in many brain regions and at nerve-muscle contacts. GABAA receptors (GABAAR) are the targets for many important drugs, including antiepileptics, sedatives and general anesthetics. One current project in the lab is focused on determining the diversity of general anesthetic biding sites in GABAARs, which will provide a basis for the development of anesthetics with fewer undesirable side effects.

Nicotinic acetylcholine receptors (nAChR), which are the site of binding of nicotine, are involved in the regulation of sleep, attention, learning, and memory. Dysfunctions of nAChRs are implicated in disorders including Alzheimer’s and Parkinson’s, and drugs that target nAChRs have potential uses in the treatment of these conditions as well as nicotine addiction. nAChRs on skeletal muscle mediate neural control of muscle contraction, and they are the receptors that are destroyed in an autoimmune disease, myasthenia gravis.  Currently the Cohen lab is studying the mechanisms of novel classes of drugs that act as enhancers of brain or muscle nAChRs.

Publications View
Enantiomeric barbiturates bind distinct inter- and intrasubunit binding sites in a nicotinic acetylcholine receptor (nAChR).
Authors: Authors: Yu Z, Cohen JB.
J Biol Chem
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Synthesis and pharmacological evaluation of neurosteroid photoaffinity ligands.
Authors: Authors: Savechenkov PY, Chiara DC, Desai R, Stern AT, Zhou X, Ziemba AM, Szabo AL, Zhang Y, Cohen JB, Forman SA, Miller KW, Bruzik KS.
Eur J Med Chem
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General Anesthetic Binding Sites in Human a4ß3d ?-Aminobutyric Acid Type A Receptors (GABAARs).
Authors: Authors: Chiara DC, Jounaidi Y, Zhou X, Savechenkov PY, Bruzik KS, Miller KW, Cohen JB.
J Biol Chem
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Photolabeling a Nicotinic Acetylcholine Receptor (nAChR) with an (a4)3(ß2)2 nAChR-Selective Positive Allosteric Modulator.
Authors: Authors: Hamouda AK, Deba F, Wang ZJ, Cohen JB.
Mol Pharmacol
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Images in Anesthesiology: An Unexpected Embolism during a Craniotomy.
Authors: Authors: Serdiuk A, Khalil F, Cohen JB.
Anesthesiology
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Multiple Non-Equivalent Interfaces Mediate Direct Activation of GABAA Receptors by Propofol.
Authors: Authors: Eaton MM, Germann AL, Arora R, Cao LQ, Gao X, Shin DJ, Wu A, Chiara DC, Cohen JB, Steinbach JH, Evers AS, Akk G.
Curr Neuropharmacol
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Positive and Negative Allosteric Modulation of an a1ß3?2 ?-Aminobutyric Acid Type A (GABAA) Receptor by Binding to a Site in the Transmembrane Domain at the ?+-ß- Interface.
Authors: Authors: Jayakar SS, Zhou X, Savechenkov PY, Chiara DC, Desai R, Bruzik KS, Miller KW, Cohen JB.
J Biol Chem
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Desformylflustrabromine (dFBr) and [3H]dFBr-Labeled Binding Sites in a Nicotinic Acetylcholine Receptor.
Authors: Authors: Hamouda AK, Wang ZJ, Stewart DS, Jain AD, Glennon RA, Cohen JB.
Mol Pharmacol
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Multiple propofol-binding sites in a ?-aminobutyric acid type A receptor (GABAAR) identified using a photoreactive propofol analog.
Authors: Authors: Jayakar SS, Zhou X, Chiara DC, Dostalova Z, Savechenkov PY, Bruzik KS, Dailey WP, Miller KW, Eckenhoff RG, Cohen JB.
J Biol Chem
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Photoaffinity labeling of nicotinic receptors: diversity of drug binding sites!
Authors: Authors: Hamouda AK, Jayakar SS, Chiara DC, Cohen JB.
J Mol Neurosci
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