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| Andres L. Buonanno, Ph.D., Senior Investigator |
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Dr. Buonanno received his Ph.D. in Molecular Biology from Washington University in St. Louis where he worked with John Merlie on the initial cloning of acetylcholine receptor genes, and studying their transcriptional regulation by electrical activity and during development. In 1988 he moved to NIH, where his group was involved in the initially cloning and characterization of glutamate receptors. His lab focused on the identification of transcription factors that regulate developmental and activity-dependent expression of NMDA receptors and muscle genes. In 1999 Dr. Buonanno became a Senior Investigator. His group presently studies the role of the Neuregulin-ErbB receptor signaling pathway, recently associated with psychiatric disorders, in neural development, synaptic plasticity and behavior.
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Staff:
- Briony Catlow, Ph.D., Contractor catlowbj@mail.nih.gov
- Paul A. Herman, Ph.D., MSN, C-RNP, (301) 451-0940 hermanpa@mail.nih.gov
- Irina Karavanova, Ph.D., Biologist, (301) 594-4641 karavani@mail.nih.gov
- Ryoichi Kimura, Ph.D., Visiting Fellow kimurary@mail.nih.gov
- Joerg Neddens, Ph.D., Visiting Fellow neddensj@mail.nih.gov
- Claudia Colina Prisco, Ph.D., Visiting Fellow, (301) 451-0945 colinapriscocn@mail.nih.gov
- Alon Shamir, Ph.D., Visiting Fellow shamiral@mail.nih.gov
- Dr. Detlef Vullhorst, Ph.D., Senior Research Fellow vullhord@mail.nih.gov
Research Interests:
Neuregulin-ErbB Signaling Regulates Neuronal Activity: Relevance for Psychiatric Disorders
Neuregulins are a family of trophic and differentiation factors that signal via ErbB receptor tyrosine kinases. Polymorphisms in the Neuregulin1 (NRG1) and ErbB4 genes have been associated with an increased risk of schizophrenia and bipolar disorder. Importantly, a NRG1 polymorphism is associated with poor cognitive function, an endophenotype associated with these psychiatric disorders. We, and others, have shown that NRG/ErbB signaling regulates the expression of neurotransmitter receptors (for glutamate, GABA and acetylcholine), myelination, and neuronal migration. We found that activation of the NRG signaling pathway reverses long-term potentiation (LTP) at glutamatergic synapses. This is an intriguing finding given the importance of LTP for memory and cognition, and because of proposed deficits in glutamate neurotransmission associated with schizophrenia. Importantly, we recently demonstrated that NRG-1 elicits its effects on LTP by modulating the levels of dopamine, which in turn activates D4 receptors, a member of the group of dopamine D2-type receptors that are the main targets of many antipsychotics (e.g. clozapine).
Our laboratory is also studying the effects of NRGs on neural network activity, in collaboration with Dr. Andre Fisahn's lab at the Karolinska Institute. We found that NRG1 dramatically increases the power of hippocampal gamma oscillations without affecting the frequency. Our immunohistochemical analyses suggest that NRG1 actions on LTP reversal and network activity are mediated via ErbB4-positive inhibitory interneurons.
The novel functional link between NRG1, dopamine and glutamate, that appears to be mediated through ErbB4-expressing GABAergic interneurons, helps to understand the behavioral alterations observed in mice expressing reduced levels of NRG and ErbB4. Given the association of NRG1 and ErbB4 with schizophrenia, and the imbalances in glutamatergic and dopaminergic transmission associated with the disorder, our results could have important implications for understanding how the NRG signaling pathway may be altered in psychiatric disorders.
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Contact Information:
Dr. Andres L. Buonanno
Laboratory of Developmental Neurobiology, NICHD
Porter Neuroscience Research Center
Building 35, Room 2C-1000
35 Convent Drive
Bethesda, MD 20892-
Telephone: (301) 496-0170 (office),
(301) 496-9939 (fax)
Email: buonanno@helix.nih.gov
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