Professor - Department of Neuroscience Professor - Menninger Department of Psychiatry & Behavioral Sciences Ph.D., University of Minnesota, 1980 One Baylor Plaza Baylor College of Medicine Houston TX, 77030 Telephone: 713-798-3710 - Fax: 713-798-3946 Email: jdani@bcm.edu Website: neuro.bcm.edu/danilab

Research in my laboratory arises from the following hypothesis: Fundamental mechanisms that serve during the normal functioning of the brain can be misdirected during neuronal disease and can be commandeered by drugs during addiction. In recent years our work has focused on processes that usurp the fundamental mechanisms underlying learning and memory. For example, we have shown that addictive drugs induce synaptic potentiation of dopamine pathways as an early step along the route to addiction. We are also investigating declining memory functions of the hippocampus during exposure to drugs or during degenerative disease, such as Alzheimer's dementia.

Work in my laboratory employs a multidisciplinary approach using cellular and higher-level systems techniques. Various electrophysiological techniques, optical signaling, immunocytochemistry, and amperometric/voltammetric measures of neurotransmitter release are applied to model systems such as tissue culture and brain slices to gain experimental advantages while investigating ion channels, receptors, synapses, neurons, and small collections of neurons. In vivo recordings with multiple tetrodes to follow neuronal units or to stimulate and record field responses are coupled to in vivo microdialysis recordings from freely-moving rats, wild-type mice, and mutant mice to pursue systems level questions that have more immediate relevance to disease and addiction.

A general goal is to understand the synaptic mechanisms that normally shape behavior, and we are moving toward that goal by considering the interactions of diffuse neurotransmitters in midbrain and limbic regions.

(1) We recently showed that endogenous cholinergic activity potently regulates dopamine release in the striatum. Those studies also have revealed a fundamental shift in the serotonin and dopamine interactions caused by antidepressant drugs.

(2) We are expanding studies into cocaine, alcohol, and nicotine addiction. Specifically, we are examining how these drugs act initially at receptors and neurons to influence broad changes in synaptic events. Our multidisciplinary approach has produced convincing evidence that addictive drugs induce synaptic plasticity like that seen during learning.

(3) We also have developed a valuable in vivo procedure for evaluating the synaptic plasticity underlying learning and memory in freely moving rats and mice. Our preliminary results indicate that long-range signaling from dopamine centers enables forms of hippocampal in vivo synaptic plasticity that underlie learning and memory.

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Jianrong Tang and John A. Dani. Dopamine Enables In Vivo Synaptic Plasticity Associated with the Addictive Drug Nicotine. Neuron 2009 Sep;63:673-682.

Zhang L, Doyon WM, Clark JJ, Phillips PE, Dani JA. Controls of tonic and phasic dopamine transmission in the dorsal and ventral striatum. Mol Pharmacol. 2009 Aug;76(2):396-404.

Zhang T, Zhang L, Liang Y, Siapas AG, Zhou FM, Dani JA. Dopamine signaling differences in the nucleus accumbens and dorsal striatum exploited by nicotine. J Neurosci. 2009 Apr 1;29(13):4035-43.

Dani JA, Bertrand D (2007) Nicotinic acetylcholine receptors and nicotinic cholinergic mechanisms of the central nervous system. Annual Reviews Pharmacology Toxicology 47:699-729.

Dani JA and Montague PR (2007) Disrupting addiction through the loss of drug-associated internal states. Nature Neuroscience 10:403-404.

Pidoplichko VI, Dani JA (2006) Acid-sensitive ionic channels in midbrain dopamine neurons are sensitive to ammonium, which may contribute to hyperammonemia damage. Proc Natl Acad Sci USA 103:11376-11380.

Dani JA, Harris RA (2005) Nicotine addiction and comorbidity with alcohol abuse and mental illness. Nature Neuroscience 8:1465-1470.

Zhou FM, Liang Y, Salas R, Zhang L, De Biasi M, Dani JA. (2005) Corelease of dopamine and serotonin from striatal dopamine terminals. Neuron 46:65-74.

Ge S, Dani JA (2005) Nicotinic acetylcholine receptors at glutamate synapses facilitate long-term depression or potentiation. J Neuroscience 25:6084-6091.

Dani JA, Zhou FM (2004) Selective dopamine filter of glutamate striatal afferents. Neuron 42:522-524.

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Jacob Javits Neuroscience Award from the National Institutes of Health, National Inst. of Neurological Disorders & Stroke

Wiersma Visiting Professorship Dept of Biology, California Institute of Technology

National Institutes of Health, New Investigator Research Award

DeBakey Award for outstanding research from Baylor College of Medicine

Bacaner Basic Science Award for excellence in research from Minnesota Medical Foundation

Distinguished Achievement Award, College of Engineering, University of Michigan

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• Danny Jenson (Neuroscience)
• Alycia Yarnall (Neuroscience)

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In Vivo LTP in Freely Moving Mice. In vivo study of synaptic plasticity that underlies learning and memory. Using freely-moving mice, we place a stimulating electrode into the angular bundle of perforant path, which relays massive information from the cortex to the hippocampus. The synaptic events are recorded in the hilus of dentate gyrus. The electrical traces show synaptic transmission before (gray) and after (red) induction of long-term potentiation of the perforant path.

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