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
Identification of binding sites in the nicotinic acetylcholine receptor for TDBzl-etomidate, a photoreactive positive allosteric effector.
Authors: Authors: Nirthanan S, Garcia G, Chiara DC, Husain SS, Cohen JB.
J Biol Chem
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Altered emotional interference processing in affective and cognitive-control brain circuitry in major depression.
Authors: Authors: Fales CL, Barch DM, Rundle MM, Mintun MA, Snyder AZ, Cohen JD, Mathews J, Sheline YI.
Biol Psychiatry
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The MATRICS Consensus Cognitive Battery, part 1: test selection, reliability, and validity.
Authors: Authors: Nuechterlein KH, Green MF, Kern RS, Baade LE, Barch DM, Cohen JD, Essock S, Fenton WS, Frese FJ, Gold JM, Goldberg T, Heaton RK, Keefe RS, Kraemer H, Mesholam-Gately R, Seidman LJ, Stover E, Weinberger DR, Young AS, Zalcman S, Marder SR.
Am J Psychiatry
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Identifying the lipid-protein interface of the alpha4beta2 neuronal nicotinic acetylcholine receptor: hydrophobic photolabeling studies with 3-(trifluoromethyl)-3-(m-[125I]iodophenyl)diazirine.
Authors: Authors: Hamouda AK, Sanghvi M, Chiara DC, Cohen JB, Blanton MP.
Biochemistry
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[3H]Benzophenone photolabeling identifies state-dependent changes in nicotinic acetylcholine receptor structure.
Authors: Authors: Garcia G, Chiara DC, Nirthanan S, Hamouda AK, Stewart DS, Cohen JB.
Biochemistry
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Identification of a GABAA receptor anesthetic binding site at subunit interfaces by photolabeling with an etomidate analog.
Authors: Authors: Li GD, Chiara DC, Sawyer GW, Husain SS, Olsen RW, Cohen JB.
J Neurosci
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Mapping the structural requirements for nicotinic acetylcholine receptor activation by using tethered alkyltrimethylammonium agonists and antagonists.
Authors: Authors: Stewart DS, Chiara DC, Cohen JB.
Biochemistry
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Synthesis of trifluoromethylaryl diazirine and benzophenone derivatives of etomidate that are potent general anesthetics and effective photolabels for probing sites on ligand-gated ion channels.
Authors: Authors: Husain SS, Nirthanan S, Ruesch D, Solt K, Cheng Q, Li GD, Arevalo E, Olsen RW, Raines DE, Forman SA, Cohen JB, Miller KW.
J Med Chem
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alpha-Conotoxin GI benzoylphenylalanine derivatives. (1)H-NMR structures and photoaffinity labeling of the Torpedo californica nicotinic acetylcholine receptor.
Authors: Authors: Kasheverov IE, Chiara DC, Zhmak MN, Maslennikov IV, Pashkov VS, Arseniev AS, Utkin YN, Cohen JB, Tsetlin VI.
FEBS J
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Cholesterol interacts with transmembrane alpha-helices M1, M3, and M4 of the Torpedo nicotinic acetylcholine receptor: photolabeling studies using [3H]Azicholesterol.
Authors: Authors: Hamouda AK, Chiara DC, Sauls D, Cohen JB, Blanton MP.
Biochemistry
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