Neurosciences Seminar Series

Unless noted otherwise, all seminars are held 4:00 p.m. to 5:00 p.m. at:
The Scripps Research Institute, La Jolla, CA
THE COMMITTEE Lecture Hall
The Skaggs Institute Building (MBB)

Upcoming Events

Wednesday, December 03, 2008

A Role for NADPH Oxidase in Pharmacological Models of Schizophrenia

M. Margarita Behrens, PhD

Associate Project Scientist
Division of Geriatrics
Department of Medicine
University of California, San Diego
La Jolla, CA 92037

Host: Bruno Conti, PhD
Contact: Floriska Chizer, (858) 784-7226

Accumulating evidence suggests that a hypofunction of NMDA-type glutamate receptors, causes or contributes to the full symptomatology of schizophrenia. It has been proposed that the reduction of the NMDA-dependent excitatory drive onto inhibitory (GABAergic) inputs results in disruption of the tonic inhibitory influence of GABA on cortical activity, and that this resulting disinhibition plays a pivotal role in the disease. Several GABAergic markers are decreased in the subset of parvalbumin (PV)-positive interneurons in the prefrontal cortex and hippocampus in autopsy material from schizophrenic subjects. The PV-positive interneurons serve a vital role in modulating cortical output and are believed to affect the postnatal development of cortical circuitry by feedforward and feedback inhibition of active pyramidal neurons. We have shown that the effects of NMDA receptor antagonists on PV-interneurons can be fully reproduced in a primary culture system composed of only excitatory and inhibitory neurons, suggesting that inputs coming from outside the cortex, such as dopamine, are not involved in this process. In trying to understand the mechanisms behind the effects of these antagonists on GABAergic circuits, we recently reported that one of the initial effects of exposure to ketamine, both in vivo and in vitro, is the activation of the superoxide producing enzyme NADPH oxidase. We will discuss the mechanism by which the initial disinhibition caused by NMDA receptor antagonists leads to the activation and induction of NADPH oxidase.

Wednesday, December 17, 2008

Regulatory RNA

Claes Wahlestedt, PhD

Professor
Director Neuroscience Discovery
The Scripps Research Institute
Jupiter, Florida

Host: Loren (Larry) Parsons, Ph.D.
Contact: Floriska Chizer, (858) 784-7226

Recent large scale transcriptomics efforts involving us (1, 2) and others have revealed a surprising but consistent finding that the majority of the mammalian genome is transcribed in vivo. Yet, protein coding sequences occupy only around 1-2 percent of the human genome. So what is all this seemingly extraneous noncoding RNA material for? Evidence is now rapidly accumulating that a significant portion of noncoding RNAs serves a regulatory function involving all areas of biology.

We have proposed that neural tissues may require the unique information coding capacities of regulatory noncoding RNAs to help elaborate the sensing, processing, computing, and control features necessary to drive the brain’s highly complex activities (3).

This presentation will focus on some implications of three growing bodies of evidence: 1) accumulating reports of large and expanding numbers of functional noncoding RNAs in the mammalian genome; 2) studies indicating that noncoding RNAs function to regulate biological systems, resulting in more adaptable and complex information processing than previously recognized; and 3) novel functionalities for noncoding RNAs, important in the molecular mechanisms of neuroscience.

Recent results from our laboratory indicate the possible functional involvement of regulatory RNAs in several human diseases including Alzheimer’s disease (4), fragile X syndrome (5) and schizophrenia. We argue that noncoding RNAs should be increasingly considered as vital components in the context of improving our understanding human diseases.

Because of the diverse regulatory roles of small and long noncoding RNAs, these molecules may not only be of interest as drug targets, but they may also prove to be important early biomarkers of emerging disease processes.

Wednesday, January 07, 2009

Genetics of Substance Dependence

Joel Gelernter, MD

Professor of Psychiatry, Genetics, and Neurobiology
Yale University School of Medicine
West Haven, CT

Host: Cindy Ehlers, Ph.D.
Contact: Floriska Chizer, (858) 784-7226

Wednesday, February 04, 2009

Micro-Managing Addiction: MicroRNAs

Paul J. Kenny, PhD

Associate Professor
Department of Molecular Therapeutics
The Scripps Research Institute
Jupiter, FL

Host: Loren (Larry) Parsons, Ph.D.
Contact: Floriska Chizer, (858) 784-7226

MicroRNAs are emerging as key regulators of neuroplasticity and brain function. In this talk I will present data demonstrating that microRNA expression is dysregulated in the dorsal striatum of rats that develop escalated levels of cocaine-taking. Further, I will show that striatal overexpression of one of these microRNAs decreases, whereas its knockdown increases, the motivation to compulsively consume cocaine. This escalation-associated microRNA is shown to dramatically amplify cAMP response element-binding protein (CREB) signaling, which in striatum is known to switch cocaine from a rewarding to aversive drug. Intriguingly, I will present data demonstrating that expression of this microRNA is reduced in striatum from human cocaine addicts compared with controls. These data reveal striatal microRNAs as novel regulators of CREB signaling that may protect against the development of compulsive cocaine-taking. Moreover, this protective mechanism may be compromised in human cocaine addicts, and may play a key role in vulnerability to addiction.

Wednesday, February 25, 2009

TBD

Paul Vezina, PhD

Associate Professor
Department of Psychiatry
University of Chicago
Chicago, IL

Host: George Koob, Ph.D.
Contact: Floriska Chizer, (858) 784-7226

Wednesday, March 18, 2009

TBD

Lars Terenius, PhD

Department of Clinical Neuroscience
Karolinska Institute
Stockholm, Sweden

Host: Loren (Larry) Parsons, Ph.D.
Contact: Floriska Chizer, (858) 784-7226

Wednesday, April 29, 2009

TBD

Marina Picciotto, PhD

Department of Psychiatry
Yale University
New Haven, CT

Host: Pietro Sanna, M.D.
Contact: Floriska Chizer, (858) 784-7226