Mechanisms of Dopamine Transmission in the VTA
CIT ID: 7090
Program date: Monday, September 08, 2008, 12:00:00 PM
Presented by: John Williams, Ph.D., Oregon Health Science University, Vollum Institute
Abstract:
Dendritic release of dopamine in the ventral tegmental area acts on D2-dopamine receptors to mediate an inhibitory postsynaptic current (IPSC). This study examines how the rise and fall in extracellular dopamine regulates the kinetics of the IPSC. Extracellular dopamine was measured electrochemically during simultaneous recording of the IPSC. Both the rise and fall of dopamine were rapid relative to the IPSC, suggesting that G-protein dependent potassium channel activation determined the time course of the IPSC. The kinetics of D2 receptor dependent activation of potassium currents was studied using outside-out patch recordings and rapid application of dopamine. Dopamine applied at a minimum concentration of 10 µM for a maximum of 100 ms mimicked the IPSC. Shorter applications of higher concentrations did not change the kinetics of the outward current. These measurements were used to construct a model predicting that dopamine travels less then 500 nm from the site of release before binding to D2 receptors.
Selected Publications:
Dang, V.C. and Williams, J.T. (2004)
Chronic morphine treatment reduces recovery from opioid desensitization. J. Neurosci. 24:7699-7706.
Beckstead, M.J., Grandy, D.K., Wickman, K., and Williams, J.T. (2004)
Vesicular dopamine release elicits an inhibitory postsynaptic current in midbrain dopamine neurons. Neuron 42:939-946.
Dumont, E.C. and Williams, J.T. (2004)
Noradrenaline triggers GABAA-inhibition of bed nucleus of the stria terminalis neurons projecting to the ventral tegmental area. J. Neurosci. 24:8198-8204.
Paladini, C.A., Mitchell, J.M., Williams, J.T., and Mark, G.P. (2004)
Cocaine self-administration selectively decreases noradrenergic regulation of metabotropic glutamate receptor-mediated inhibition in dopamine neurons.
J. Neurosci. 24:5209-5215.
Paladini, C.A. and Williams, J.T. (2004)
Noradrenergic inhibition of midbrain dopamine neurons. J. Neurosci. 24:4568-4575.
Paladini, C.A., Robinson, S., Morikawa, H., Williams, J.T., and Palmiter, R. (2003) Dopamine controls the firing pattern of dopamine neurons via a network feedback mechanism.
Proc. Natl. Acad. Sci. USA 100:2866-2871.
For more information see our website - http://neuroseries.info.nih.gov
Audio Podcasts |
|
Video Podcasts |
|
Description |
Runtime |
|
|
Description |
Runtime |
|
Enhanced Audio Podcast
|
55:46
|
|
|
Enhanced Video Podcast
|
55:46
|
|
Dying Young as Late as Possible: Planarians, Regeneration and Stem Cells
CIT ID: 6984
Program date: Wednesday, September 03, 2008, 3:00:00 PM
Presented by: Alejandro Sanchez Alvarado, HHMI Investigator, University of Utah School of Medicine
Abstract:
TALK SUMMARY: It is paradoxical that for many animal (including humans), the apparent anatomical stability of their adult bodies is maintained by constant change. Under normal physiological conditions, the functions of many organs depend on the continuous destruction and renewal of their cells. Equally remarkable is the fact the adult tissues and organs of many organisms can be fully restored after amputation.
In fact, it appears that metazoans have evolved a series of renewal and repair mechanisms to respond to both trauma and normal wear and tear. Moreover, these mechanisms are under tight regulatory control such that organismal form and function can be maintained throughout life. As important as repair and restoration are to survival of multicellular organisms, we know little about how these processes are effected and regulated at the cellular and molecular levels.
Here, I will discuss how the study of a simple metazoan, the planarian Schmidtea mediterranea, is beginning to shed light on the way adult animals regulate tissue homeostasis and the replacement of the body parts lost to injury.
BIOGRAPHICAL SKETCH: Alejandro Sanchez Alvarado was born in Caracas, Venezuela. He received his Bachelor's Degree in Molecular Biology and Chemistry from Vanderbilt University in 1986. In 1992, he received his Ph.D. in Pharmacology and Cell Biophysics at the University of Cincinnati School of Medicine, where he studied mouse ES cells and their in vitro differentiation under the tutelage of Dr. Jeffrey Robbins and Thomas Doetschman.
In 1994, he joined the laboratory of Dr. Donald Brown at the Carnegie Institution of Washington Department of Embryology as a postdoctoral fellow, and in 1995 was appointed Staff Associate. It was during third period that Dr. Sanchez Alvarado began to explore system in which to molecularly dissect the problem of regeneration. In 2002 he became an Associate Professor at the Department of Neurobiology and Anatomy at the University of Utah School of Medicine, and in 2005 he was promoted to Professor and appointed a Howard Hughes Medical Institute Investigator. His current efforts are aimed at elucidating the molecular basis of regeneration using the free-living flatworm Schmidtea mediterranea.
For more information, visit http://planaria.neuro.utah.edu/
Audio Podcasts |
|
Video Podcasts |
|
Description |
Runtime |
|
|
Description |
Runtime |
|
Enhanced Audio Podcast
|
1:11:05
|
|
|
Enhanced Video Podcast
|
1:11:05
|
|
How to Give an Effective Job Talk
CIT ID: 6911
Program date: Monday, June 30, 2008, 9:00:00 AM
Presented by: Sharon Milgram, Director of the Office of Training & Education
Abstract:
Are you a postdoctoral fellow just beginning your job search? Would you like to learn how give effective job talks in academic or industry settings? This seminar will provide you with valuable insight into giving an outstanding, memorable job talk for a variety of audiences. Learn important elements to be included in any job talk, tips on giving a successful academic "chalk talk," how to structure your talk for your specific audience, and more!
Audio Podcasts |
|
Video Podcasts |
|
Description |
Runtime |
|
|
Description |
Runtime |
|
Enhanced Audio Podcast
|
1:57:09
|
|
|
Enhanced Video Podcast
|
1:57:09
|
|
Immune Regulation in the Intestine
CIT ID: 6741
Program date: Wednesday, June 25, 2008, 3:00:00 PM
Presented by: Fiona Powrie
Abstract:
The gastrointestinal tract in humans is colonised by a large number and diverse array of commensal bacteria many of which are beneficial to the host. Most of reside peacefully with our gut residents however a breakdown in intestinal homeostasis can result in inflammatory diseases of the intestine including inflammatory bowel disease, celiacs disease and allergy.
In this talk I will review recent work from my own laboratory and others that indicate the intestinal homeostasis is a delicate balance between pro-inflammatory effector responses and immune suppressive regulatory T cells.
Analysis of cytokines that drive intestinal inflammation identified IL23 as a master regulator that orchestrates intestinal inflammation via effects on innate cells and T cells. Recent genome wide-association studies have identified polymorphisms in the IL23R as linked to susceptibility to IBD validating IL23 mediated pathways as potential therapeutic targets in IBD.
BIOGRAPHICAL SKETCH: Fiona Powrie started her career as a D.Phil student with Don Mason in Oxford before finishing her training as postdoctoral fellow with Dr. R. Coffman at the DNAX research Institute in Palo Alto, California. In 1996 she returned to the UK to establish her own laboratory as a Wellcome Trust Senior Fellow. She is now Professor of Immunology at the Sir William Dunn School of Pathology , Oxford University.
Fiona Powrie’s early work identified functionally distinct subsets of CD4+ T cells that could suppress immune responses and whose absence led to inflammatory disease. In the last decade she has focused on immune regulation in the intestine. Her work has identified the functional role of regulatory T cells in intestinal homeostasis and shed light on their development and mechanism of action. She has also shown that both adaptive and innate immune mechanisms contribute to intestinal inflammation and identified the cytokine
IL23 as a pivotal player in the pathogenesis of chronic intestinal inflammation.
For more information, visit
http://www.path.ox.ac.uk/dirsci/immunology/powrie
The NIH Director's Wednesday Afternoon Lecture Series includes weekly scientific talks by some of the top researchers in the biomedical sciences worldwide.
Audio Podcasts |
|
Video Podcasts |
|
Description |
Runtime |
|
|
Description |
Runtime |
|
Enhanced Audio Podcast
|
56:05
|
|
|
Enhanced Video Podcast
|
56:05
|
|
The NIH does not endorse or recommend any
commercial products, processes, or services. The U.S. Government
does not warrant or assume any legal liability or responsibility
for the accuracy, completeness, or usefulness of any
information, apparatus, product, or process disclosed. The NIH
disclaims all warranties regarding these products, including,
but not limited to, all warranties, express or implied of
merchantability and fitness for any particular purpose. The NIH
further disclaims all obligations and liabilities for damages
arising from the use or attempted use of these products,
including but not limited to direct, indirect, special, and
consequential damages, attorneys' and experts' fees and court
costs. Any use of these products will be at the risk of the
user.
|