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The Nathan S. Kline Institute for Psychiatric Research

Neurochemistry

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Neurochemistry

Vadasz Lab

Lab Name
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Csaba Vadasz, Ph.D.
Head of Lab

The Vadasz Lab's behavioral approach is based on ethology, which is inseparable from evolution by natural selection. Because all complex traits of living organisms, including behavior, are modulated by genetic factors, our genetic selection approach models evolution to understand the genetic architecture, and to enable meaningful use of transgenic technologies in biomedicine.

History

Our Neurobehavioral Genetic Research Program originated in the late 1970s when Dr. Csaba Vadasz formed a collaboration with neurobiologists at Cornell University to investigate the genetics of the midbrain dopamine system and related behaviors. The program’s initial focus was an integration of ethology-based behavior genetic research experience and neurobiology-based research.

Mission

The overall mission of the Lab is to study the molecular-cellular-behavioral pathways involved in the inheritance of complex natural and pathological behaviors using model organisms. This is sometimes referred to as "G2BB" (Genes to Brains and Behaviors). The Lab focuses on identification of genetic factors which predispose or modulate complex behaviors (for example, substance abuse, addiction) using laboratory vertebrate organisms to model the human condition. When such factors are identified, the next steps include tests of the evolutionary conservation of the discovered genetic effect in human populations, and exploration of novel treatment avenues.

QTL and RQI

Our Lab spearheaded the Quantitative Trait Locus (QTL) mapping research in neurobiology, conceiving the principle of a new approach (Recombinant QTL Introgression or RQI)  and providing proof of principle by creating the largest congenic RQI mouse strain set for gene mapping and behavioral studies. In the early 1980s, the Lab focused on the midbrain dopamine system, which is implicated in various normal and abnormal behaviors including Parkinson's disease, attention, learning, and addiction. The research team created advanced preclinical models with different dopamine neuronal cluster size using the RQI principle. 

From Genes to Alcohol Addiction

Because of a link between dopamine and addiction, a new direction was added: mapping of genes which modulate alcohol drinking behavior. Gene mapping and bioinformatic studies on mouse chromosome 6 led to the first discovery of a gene accounting for alcohol preference in a mammalian model of voluntary alcohol drinking. Providing evidence for the efficacy of the RQI approach, it identified a gene Grm7 (glutamate receptor metabotropic, subtype 7) and characterized it as a cis-regulated gene. The discovery was first announced by an NIH news release. Explaining a link between the two research directions it was recently reported that midbrain dopamine cells (MBDOP2) express Grm7.

The current direction of the Neurobehavioral Genetic Research Program includes characterization of the Grm7 gene, and human genetic studies on the role of the mGlu7 receptor in addiction.