Cold Spring Harbor Researchers Awarded $200,000 in Research Grants

The National Alliance for Research on Schizophrenia and Depression (NARSAD) awarded $100,000 Independent Investigator grants to Grigori Enikolopov, Ph.D., and Zachary Mainen, Ph.D., both of Cold Spring Harbor Laboratory. The awards were announced in July, with funding starting September 15, 2004. Dr. Enikolopov’s neural stem cell research should further understanding of the neural basis for depression, and Dr. Mainen will embark on a schizophrenia-related neuroscience study in rats.

NARSAD's Independent Investigator Awards are two-year research grants of up to $50,000 per year (to a maximum of $100,000 for two years), provided to scientists at the associate professor level or equivalent. These researchers must have already won national competitive support as principal investigators. Both basic research and clinical projects are supported, but studies must be innovative and relevant to schizophrenia, major affective disorders, or other serious mental illnesses. Since 1995, 367 Independent Investigator grants have been awarded.

Project Title: A Novel Approach to Assess Changes in Neurogenesis in Response to Psychotropic Drugs and Transplantation
Grigori Enikolopov, Ph.D., of Cold Spring Harbor Laboratory, using a mouse model, will attempt to develop and approach for quantitative assessment and comparison of the properties of neural stem cells, as it is necessary for new neurons to be generated from stem cells in the brain in order for antidepressant drugs to work. Neural stem cells role in the functioning adult brain is still unclear and Dr. Enikolopov will study neural cells at various stages of their differentiation program to ascertain the effects antidepressant drugs on neural stem cells. He will also assess the properties of stem cells after they are transplanted into a lesioned nervous system. These studies will allow for rigorous measurements of what happens to neural stem cells in the adult brain and will further understanding of the cellular basis of depression.

Project Title: Direct Monitoring Prefrontal Cortical Circuit Function in an Animal Model of Schizophrenia
Zachary F. Mainen, Ph.D., of Cold Spring Harbor Laboratory,
proposes using a novel method, single neuron cell recording, to test in the cortex of awake rats the effects on neurotransmission of ketamine, an abused substance that can produce schizophrenia-like symptoms in humans. Evidence suggests ketamine produces its psychotomimetic effects by possibly blocking the NMDA glutamate receptors on inhibitory neurons in the prefrontal cortex. The hypothesis can explain why blocking an excitatory receptor can decrease prefrontal activity. This hypothesis can also link the NMDA receptor hypofunction theory of schizophrenia with evidence for reductions in GABA function in human schizophrenics. In the proposed study, Dr. Mainen will research the role of the neurotransmitters glutamate and GABA in the neural pathology underlying schizophrenia. Early results reveal that the laboratory can distinguish inhibitory interneurons and excitatory pyramidal neurons on the basis of their spike waveforms. They also demonstrate that the lab can assay local inhibitory circuits. These established metrics should allow directly testing of the hypothesis that NMDA receptor antagonists (ketamine) disrupt the functioning of neocortical circuitry by suppressing the activity of fast-spiking GABAergic interneurons.

NARSAD is a nonprofit charitable organization that raises funds from individuals, corporations and foundations. It does not accept government funding. Since its founding in 1987, NARSAD has raised more than $162.1 million. Over the years, it has funded more than 2,400 research projects by over 1,900 emerging and established scientists at 323 universities and medical research institutions. In 2004 alone, NARSAD will fund 674 scientists at top research universities in the U.S. and abroad.

NARSAD’s administrative expenses are underwritten by two family foundations, enabling the organization to direct 100 percent of every dollar it raises from donors to support research. Grants are not limited to the study of schizophrenia and depression, but span a wide range of serious mental illnesses and brain diseases, including bipolar disorder, anxiety disorders, and autism. For more information on NARSAD and its activities, please call 516.487.6930 or visit www.narsad.org.

Cold Spring Harbor Laboratory is a private, non-profit basic research institution. Under the leadership of Dr. Bruce Stillman, a member of the National Academy of Sciences and a Fellow of the Royal Society (London), more than 330 scientists at the Laboratory conduct groundbreaking research in cancer, neurobiology, plant genetics, and bioinformatics. For more information, visit www.cshl.edu.