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
Identifying barbiturate binding sites in a nicotinic acetylcholine receptor with [3H]allyl m-trifluoromethyldiazirine mephobarbital, a photoreactive barbiturate.
Authors: Authors: Hamouda AK, Stewart DS, Chiara DC, Savechenkov PY, Bruzik KS, Cohen JB.
Mol Pharmacol
View full abstract on Pubmed
Photoaffinity labeling the propofol binding site in GLIC.
Authors: Authors: Chiara DC, Gill JF, Chen Q, Tillman T, Dailey WP, Eckenhoff RG, Xu Y, Tang P, Cohen JB.
Biochemistry
View full abstract on Pubmed
Specificity of intersubunit general anesthetic-binding sites in the transmembrane domain of the human a1ß3?2 ?-aminobutyric acid type A (GABAA) receptor.
Authors: Authors: Chiara DC, Jayakar SS, Zhou X, Zhang X, Savechenkov PY, Bruzik KS, Miller KW, Cohen JB.
J Biol Chem
View full abstract on Pubmed
Identification of propofol binding sites in a nicotinic acetylcholine receptor with a photoreactive propofol analog.
Authors: Authors: Jayakar SS, Dailey WP, Eckenhoff RG, Cohen JB.
J Biol Chem
View full abstract on Pubmed
Physostigmine and galanthamine bind in the presence of agonist at the canonical and noncanonical subunit interfaces of a nicotinic acetylcholine receptor.
Authors: Authors: Hamouda AK, Kimm T, Cohen JB.
J Neurosci
View full abstract on Pubmed
Bone cement embolism.
Authors: Authors: Cohen JB.
Anesthesiology
View full abstract on Pubmed
Allyl m-trifluoromethyldiazirine mephobarbital: an unusually potent enantioselective and photoreactive barbiturate general anesthetic.
Authors: Authors: Savechenkov PY, Zhang X, Chiara DC, Stewart DS, Ge R, Zhou X, Raines DE, Cohen JB, Forman SA, Miller KW, Bruzik KS.
J Med Chem
View full abstract on Pubmed
Bupropion binds to two sites in the Torpedo nicotinic acetylcholine receptor transmembrane domain: a photoaffinity labeling study with the bupropion analogue [(125)I]-SADU-3-72.
Authors: Authors: Pandhare A, Hamouda AK, Staggs B, Aggarwal S, Duddempudi PK, Lever JR, Lapinsky DJ, Jansen M, Cohen JB, Blanton MP.
Biochemistry
View full abstract on Pubmed
Mapping general anesthetic binding site(s) in human a1ß3 ?-aminobutyric acid type A receptors with [³H]TDBzl-etomidate, a photoreactive etomidate analogue.
Authors: Authors: Chiara DC, Dostalova Z, Jayakar SS, Zhou X, Miller KW, Cohen JB.
Biochemistry
View full abstract on Pubmed
p-(4-Azipentyl)propofol: a potent photoreactive general anesthetic derivative of propofol.
Authors: Authors: Stewart DS, Savechenkov PY, Dostalova Z, Chiara DC, Ge R, Raines DE, Cohen JB, Forman SA, Bruzik KS, Miller KW.
J Med Chem
View full abstract on Pubmed