NARSAD Funds Two Cold Spring Harbor Laboratory Researchers

The National Alliance for Research on Schizophrenia and Depression is providing $120,000 in 2004 to two Cold Spring Harbor Laboratory researchers to study causes and treatments for mental illness. Neuronal pathways in schizophrenia and brain development are the research topics NARSAD is supporting this year at Cold Spring Harbor.

NARSAD, the largest donor-supported organization in the world devoted exclusively to funding scientific research on psychiatric disorders, is awarding two (2), two-year Young Investigator awards to the Cold Spring Harbor community.

Since the inception of its programs in 1987, NARSAD has awarded $157.3 million to fund 2,364 grants at 321 universities and medical research institutions in the United States and 22 other countries. All public contributions for research go 100 percent to research, since two family foundations provide contributions supporting all administrative and overhead expenses.

In 2004, its seventeenth year of research funding, NARSAD is awarding a total of 190 two-year/$60,000 Young Investigator awards, 6 one-year/$30,000 Young Investigator awards, and 15 Distinguished Investigator awards (one-year/$100,000). NARSAD will also be making another round of awards in July--the Independent Investigator Awards, which are two-year awards at $50,000/year.

The scientific leadership of NARSAD, the Scientific Council, reviewed over 1,000 grant applications to select these current awards. The Council includes among its membership three Nobel Prize winners, the present and four former directors of the National Institute of Mental Health and many of the most distinguished leaders in psychiatric research in the major universities and medical centers around the world.

"The research NARSAD is supporting with these grants represents all phases of the leading edge of research on the human brain and mental disorders,” says the Council's president, Herbert Pardes, M.D., who also is President & Chief Executive Officer at NewYork-Presbyterian Hospital, professor of psychiatry at Columbia University College of Physicians and Surgeons, as well as the former Vice President for Health Sciences of Columbia University and former director of the National Institute of Mental Health. “The studies we are funding will build upon recent breakthroughs in genetics, imaging technology and molecular biology of the brain.”

“Not long ago, people were looking for a single gene for each mental illness, but today as our research grants show, there is a multiplicity of genes functioning in complex relationships at the core of each of the characteristic mental illnesses,” Dr. Pardes adds. “The research we are funding aims to understand this complexity and then to treat it.”

In announcing the awards, Constance E. Lieber, President of NARSAD, said she was “proud to support the efforts of Cold Spring Harbor researchers.”

NARSAD's Young Investigator Award Program provides support for the most promising young scientists conducting neurobiological research. Basic and/or clinical investigators are supported, but research must be relevant to schizophrenia, major affective disorders, or other serious mental illnesses.

NARSAD's Distinguished Investigator Award Program provides support for experienced investigators (full professor or equivalent) conducting neurobiological research. Areas of particular interest to the Scientific Council include patient populations with unique or unusual characteristics and innovative projects that might not otherwise receive funding.

Below are synopses of the Cold Spring Harbor Young Investigator Awards:

Graziella Di Cristo, Ph.D., of Cold Spring Harbor Laboratory, notes that alterations in GABAergic circuitry of the prefrontal cortex may contribute to working memory impairment commonly observed in schizophrenic patients. These alterations appear to be in subset of GABA interneurons called PV-interneurons. But the development of GABAergic synapses is poorly understood due to their heterogeneity and the lack of high-resolution morphological markers. Dr. Di Cristo, though, has developed novel methods to visualize PV interneurons at synaptic resolution both in transgenic mice and in organotypic cortical slice cultures. She has found the development of mature pattern of perisomatic GABAergic innervation occurred in cortical slice cultures, with a time course nearly identical to that in vivo. Now, Dr. Di Cristo plans on using this experimental model to identify the cellular and molecular mechanisms underlying the development and plasticity of perisomatic GABAergic innervation. Uncovering the mechanisms governing the development and plasticity of GABAergic innervation could lead to new therapies for mental disorders, such as schizophrenia.

Edward S. Ruthazer, Ph.D., of Cold Spring Harbor Laboratory, aims to study axon branch development in the visual system of tadpoles to elucidate the basic mechanism of the brain’s structural plasticity. Using time-lapse imaging, Dr. Ruthazer has shown axonal trees are dynamic structures that add and retract branches over minutes. Axonal projection is fine-tuned through stabilization of branches that connect with correct postsynaptic partners and elimination of inappropriate contacts. Dr. Ruthazer proposes a synaptic adhesion model of axon stabilization, which hypothesizes that local stabilization of axonal shape is mediated by adhesive interactions at synaptic sites. This will be tested by in vivo time-lapse imaging of the axons of individual retinal ganglion cells that have genes expressing both yellow fluorescent protein, which fills the cell to reveal its morphology, and synaptophysin-tagged cyan fluorescent protein, which targets synaptic vesicles and marks synaptic sites in the terminal branch of the axon. A likely candidate molecule for adhesion at synapses, N-cadherin, will also be tested for its role in axon branch stabilization via expression of a mutant form of N-cadherin that interferes with the endogenous protein function in these cells.