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
The Agrin/MuSK signaling pathway is spatially segregated from the neuregulin/ErbB receptor signaling pathway at the neuromuscular junction.
Authors: Authors: Trinidad JC, Fischbach GD, Cohen JB.
J Neurosci
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Identification of sites of incorporation in the nicotinic acetylcholine receptor of a photoactivatible general anesthetic.
Authors: Authors: Pratt MB, Husain SS, Miller KW, Cohen JB.
J Biol Chem
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Identification of the sites of incorporation of [3H]ethidium diazide within the Torpedo nicotinic acetylcholine receptor ion channel.
Authors: Authors: Pratt MB, Pedersen SE, Cohen JB.
Biochemistry
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Probing the structure of the nicotinic acetylcholine receptor with 4-benzoylbenzoylcholine, a novel photoaffinity competitive antagonist.
Authors: Authors: Wang D, Chiara DC, Xie Y, Cohen JB.
J Biol Chem
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Mapping the agonist binding site of the nicotinic acetylcholine receptor. Orientation requirements for activation by covalent agonist.
Authors: Authors: Sullivan DA, Cohen JB.
J Biol Chem
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Synthesis and properties of 3-(2-hydroxyethyl)-3-n-pentyldiazirine, a photoactivable general anesthetic.
Authors: Authors: Husain SS, Forman SA, Kloczewiak MA, Addona GH, Olsen RW, Pratt MB, Cohen JB, Miller KW.
J Med Chem
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Photoaffinity labeling the torpedo nicotinic acetylcholine receptor with [(3)H]tetracaine, a nondesensitizing noncompetitive antagonist.
Authors: Authors: Middleton RE, Strnad NP, Cohen JB.
Mol Pharmacol
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Identification of amino acids of the torpedo nicotinic acetylcholine receptor contributing to the binding site for the noncompetitive antagonist [(3)H]tetracaine.
Authors: Authors: Gallagher MJ, Cohen JB.
Mol Pharmacol
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Structure of the agonist-binding sites of the Torpedo nicotinic acetylcholine receptor: affinity-labeling and mutational analyses identify gamma Tyr-111/delta Arg-113 as antagonist affinity determinants.
Authors: Authors: Chiara DC, Xie Y, Cohen JB.
Biochemistry
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The steroid promegestone is a noncompetitive antagonist of the Torpedo nicotinic acetylcholine receptor that interacts with the lipid-protein interface.
Authors: Authors: Blanton MP, Xie Y, Dangott LJ, Cohen JB.
Mol Pharmacol
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