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
Multiple transmembrane binding sites for p-trifluoromethyldiazirinyl-etomidate, a photoreactive Torpedo nicotinic acetylcholine receptor allosteric inhibitor.
Authors: Authors: Hamouda AK, Stewart DS, Husain SS, Cohen JB.
J Biol Chem
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p-Trifluoromethyldiazirinyl-etomidate: a potent photoreactive general anesthetic derivative of etomidate that is selective for ligand-gated cationic ion channels.
Authors: Authors: Husain SS, Stewart D, Desai R, Hamouda AK, Li SG, Kelly E, Dostalova Z, Zhou X, Cotten JF, Raines DE, Olsen RW, Cohen JB, Forman SA, Miller KW.
J Med Chem
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Numerous classes of general anesthetics inhibit etomidate binding to gamma-aminobutyric acid type A (GABAA) receptors.
Authors: Authors: Li GD, Chiara DC, Cohen JB, Olsen RW.
J Biol Chem
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Conformational changes in the nicotinic acetylcholine receptor during gating and desensitization.
Authors: Authors: Yamodo IH, Chiara DC, Cohen JB, Miller KW.
Biochemistry
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[(3)H]chlorpromazine photolabeling of the torpedo nicotinic acetylcholine receptor identifies two state-dependent binding sites in the ion channel.
Authors: Authors: Chiara DC, Hamouda AK, Ziebell MR, Mejia LA, Garcia G, Cohen JB.
Biochemistry
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Hydrophobic photolabeling studies identify the lipid-protein interface of the 5-HT3A receptor.
Authors: Authors: Sanghvi M, Hamouda AK, Davis MI, Morton RA, Srivastava S, Pandhare A, Duddempudi PK, Machu TK, Lovinger DM, Cohen JB, Blanton MP.
Biochemistry
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[(3)H]Epibatidine photolabels non-equivalent amino acids in the agonist binding site of Torpedo and alpha4beta2 nicotinic acetylcholine receptors.
Authors: Authors: Srivastava S, Hamouda AK, Pandhare A, Duddempudi PK, Sanghvi M, Cohen JB, Blanton MP.
J Biol Chem
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Neurosteroids allosterically modulate binding of the anesthetic etomidate to gamma-aminobutyric acid type A receptors.
Authors: Authors: Li GD, Chiara DC, Cohen JB, Olsen RW.
J Biol Chem
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Time-resolved photolabeling of the nicotinic acetylcholine receptor by [3H]azietomidate, an open-state inhibitor.
Authors: Authors: Chiara DC, Hong FH, Arevalo E, Husain SS, Miller KW, Forman SA, Cohen JB.
Mol Pharmacol
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Probing the structure of the affinity-purified and lipid-reconstituted torpedo nicotinic acetylcholine receptor.
Authors: Authors: Hamouda AK, Chiara DC, Blanton MP, Cohen JB.
Biochemistry
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