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
Site specificity of agonist-induced opening and desensitization of the Torpedo californica nicotinic acetylcholine receptor.
Authors: Authors: Andreeva IE, Nirthanan S, Cohen JB, Pedersen SE.
Biochemistry
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Imaging valuation models in human choice.
Authors: Authors: Montague PR, King-Casas B, Cohen JD.
Annu Rev Neurosci
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Cell-surface MuSK self-association: a crucial role for the putative signal sequence.
Authors: Authors: Bianchetta MJ, Betensky RA, Cohen JB.
Biochemistry
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Photolabeling the Torpedo nicotinic acetylcholine receptor with 4-azido-2,3,5,6-tetrafluorobenzoylcholine, a partial agonist.
Authors: Authors: Nirthanan S, Ziebell MR, Chiara DC, Hong F, Cohen JB.
Biochemistry
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Gating-enhanced accessibility of hydrophobic sites within the transmembrane region of the nicotinic acetylcholine receptor's {delta}-subunit. A time-resolved photolabeling study.
Authors: Authors: Arevalo E, Chiara DC, Forman SA, Cohen JB, Miller KW.
J Biol Chem
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Computational roles for dopamine in behavioural control.
Authors: Authors: Montague PR, Hyman SE, Cohen JD.
Nature
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Neuregulin inhibits acetylcholine receptor aggregation in myotubes.
Authors: Authors: Trinidad JC, Cohen JB.
J Biol Chem
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Identification of binding sites in the nicotinic acetylcholine receptor for [3H]azietomidate, a photoactivatable general anesthetic.
Authors: Authors: Ziebell MR, Nirthanan S, Husain SS, Miller KW, Cohen JB.
J Biol Chem
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Identification of nicotinic acetylcholine receptor amino acids photolabeled by the volatile anesthetic halothane.
Authors: Authors: Chiara DC, Dangott LJ, Eckenhoff RG, Cohen JB.
Biochemistry
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2-(3-Methyl-3H-diaziren-3-yl)ethyl 1-(1-phenylethyl)-1H-imidazole-5-carboxylate: a derivative of the stereoselective general anesthetic etomidate for photolabeling ligand-gated ion channels.
Authors: Authors: Husain SS, Ziebell MR, Ruesch D, Hong F, Arevalo E, Kosterlitz JA, Olsen RW, Forman SA, Cohen JB, Miller KW.
J Med Chem
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