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John Dani
Baylor College of MedicineDepartment: NeuroscienceAddress: One Baylor Plaza Baylor College of Medicine Houston TX, 77030 Phone: 713-798-3710 Fax: 713-798-3946 Email: jdani@bcm.edu Web: neuro.bcm.edu/danilab/ |
Education
University of Minnesota, 1980
Honors
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
Research Topic
Mechanisms Underlying Synaptic Communication and Plasticity
Research Description
The lab’s efforts arise from the hypothesis that fundamental mechanisms underlie the communication and adaptability of the nervous system. Those same cellular mechanisms that normally serve the brain are misdirected and damaged during disease and are commandeered and altered by drugs during addiction. Therefore, fundamental mechanisms underlying neuronal function offer points of entry for pharmacological methods aimed at relieving or preventing abnormal behaviors of mental disease and drug addiction. From this research prospective, the laboratory has made contributions toward our understanding or treatment of degenerative diseases, learning and memory, and mood disorders, but much of our effort in the last decade has been in the field of nicotine and other drug addictions. For example, we have shown that addictive drugs induce synaptic potentiation of dopamine pathways as an early step along the route to addiction and that antidepressants alter the signaling relationship between dopamine and serotonin. We are also investigating memory functions of the hippocampus during exposure to drugs and stress or during degenerative disease, such as Parkinson’s disease.
Work in the laboratory employs a multidisciplinary approach using cellular and higher-level physiological systems techniques. The lab applies various electrophysiological techniques, optical signaling, immunocytochemistry, and amperometric/voltammetric measures of neurotransmitter release to model systems such as tissue culture and brain slices to gain experimental advantages while investigating the mechanisms of ion channels, receptors, synapses, neurons, and small collections of neurons. In addition, the lab has an arsenal of in vivo recordings techniques.
We apply these in vivo techniques to freely-moving rats and mice while they perform pertinent behavioral tasks, but occasionally anesthetized preparations are also used to gain experimental advantages. We now routinely apply microdialysis and HPLC to follow neurotransmitter levels, and this and related methods are used to apply drugs and signaling molecules to specific local areas within the brain. In addition, we are using multiple kinds of in vivo electrophysiological techniques couple to RNAi approaches to manipulate signaling molecules. Another extremely valuable approach is to stimulate a particular neural pathway and record the local field potential in rats and mice. This methodology allows us to perform many of the experiments that have only previous been performed in brain slices, but we obtain the data from freely-moving rodents over the course of months. As an example of the results, we have monitored the synaptic changes (as they occur) during drug-linked associative memory. These are exciting new kinds of experiments that provide a low level endophenotype for synaptic events that are much nearer to the underlying genomic and proteomic signals than are the higher level behaviors or symptoms of genetic manipulations.
The most powerful and demanding in vivo technique is the application of multiple tetrodes to follow many neuronal units while also stimulating and recording field responses. This methodology enables us to follow, potentially, dozens of individual neurons in a circuit or in related separate circuits during behavioral events. Our recent efforts (J Neurosci. 2009, 29:4035-43) showed that dopamine signaling to the dorsal striatum and nucleus accumbens are decoded differently. Those dopamine signaling differences are a fundamental signaling aspect associated with nicotine addiction. The most recent in vivo technique being established in my lab is to use carbon-fiber electrodes to measure catecholamine concentrations using fast-scan cyclic voltammetry. This method will enable us to follow dopamine concentration changes on the sub-second time scale within small target areas of the brain during behavioral tasks. Arising from our new efforts, the lab has one of the most diverse and powerful arrays of in vitro and in vivo physiological techniques available
Selected Publications
- 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.
- 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.
- 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.
Lab Members
Lab Photos
Last edited on: September 21, 2009