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 amino acids in the nicotinic acetylcholine receptor agonist binding site and ion channel photolabeled by 4-[(3-trifluoromethyl)-3H-diazirin-3-yl]benzoylcholine, a novel photoaffinity antagonist.
Authors: Authors: Chiara DC, Trinidad JC, Wang D, Ziebell MR, Sullivan D, Cohen JB.
Biochemistry
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Identification of the bovine gamma-aminobutyric acid type A receptor alpha subunit residues photolabeled by the imidazobenzodiazepine [3H]Ro15-4513.
Authors: Authors: Sawyer GW, Chiara DC, Olsen RW, Cohen JB.
J Biol Chem
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Hyperscanning: simultaneous fMRI during linked social interactions.
Authors: Authors: Montague PR, Berns GS, Cohen JD, McClure SM, Pagnoni G, Dhamala M, Wiest MC, Karpov I, King RD, Apple N, Fisher RE.
Neuroimage
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Mapping the agonist binding site of the nicotinic acetylcholine receptor by cysteine scanning mutagenesis: antagonist footprint and secondary structure prediction.
Authors: Authors: Sullivan D, Chiara DC, Cohen JB.
Mol Pharmacol
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Interactions of the rapsyn RING-H2 domain with dystroglycan.
Authors: Authors: Bartoli M, Ramarao MK, Cohen JB.
J Biol Chem
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Identification and characterization of membrane-associated polypeptides in Torpedo nicotinic acetylcholine receptor-rich membranes by hydrophobic photolabeling.
Authors: Authors: Blanton MP, Lala AK, Cohen JB.
Biochim Biophys Acta
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Interactions between 3-(Trifluoromethyl)-3-(m-[(125)I]iodophenyl)diazirine and tetracaine, phencyclidine, or histrionicotoxin in the Torpedo series nicotinic acetylcholine receptor ion channel.
Authors: Authors: Gallagher MJ, Chiara DC, Cohen JB.
Mol Pharmacol
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Role of rapsyn tetratricopeptide repeat and coiled-coil domains in self-association and nicotinic acetylcholine receptor clustering.
Authors: Authors: Ramarao MK, Bianchetta MJ, Lanken J, Cohen JB.
J Biol Chem
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Contributions of Torpedo nicotinic acetylcholine receptor gamma Trp-55 and delta Trp-57 to agonist and competitive antagonist function.
Authors: Authors: Xie Y, Cohen JB.
J Biol Chem
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Site of resting state inhibition of the nicotinic acetylcholine receptor by a hydrophobic inhibitor.
Authors: Authors: Chiara DC, Kloczewiak MA, Addona GH, Yu JA, Cohen JB, Miller KW.
Biochemistry
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