| | Principal Investigators
| Alexei Morozov, Ph. D. |
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Dr.
Morozov is a chief of the Unit
of Behavioral Genetics in the laboratory of Molecular
Pathophysiology, Mood and Anxiety Disorder Program, National Institute of Mental Health, National Institutes of Health. Dr. Morozov received his M.S. from Lomonosov's Moscow State University, and Ph. D degree from the University of Illinois at Chicago working on the regulation of the cell cycle and transcription by viral oncoproteins. During postdoctoral fellowship with Eric Kandel at Columbia University, he employed conditional genetic manipulations to investigate the roles of the regulators of MAP kinase cascade, small GTPase Rap1 and Brain Derived Neurotrophic Factor (BDNF) in neuronal plasticity, learning and memory. By interfering with the function of Rap1, he has demonstrated that a specific pool of MAP kinase controlled by Rap1 is required for certain forms of neuronal plasticity, learning and memory. By selectively eliminating BDNF gene in the CA1, or CA1 and CA3 areas of the hippocampus, he had shown that BDNF involved in the hippocampal long-term potentiation is produced by the presynaptic neurons by targeting the same neurons. |
| Research Interests |
| Dr. Morozov's unit studies behavioral roles of molecules involved in neuronal plasticity focusing on p42/44MAP kinase, as well as BDNF and small GTPase Rap1, both of which regulate MAP kinase cascade. Assuming that "plasticity molecules" control mood and cognition, the lab is investigating their behavioral functions in specific neuronal circuits by creating mice with the knockouts restricted to those circuits. Mice with such lesions are tested as potential models of psychiatric disorders. Using this approach they have discovered that mice lacking BDNF in the forebrain develop high levels of aggression and fear representing a potential model of post-traumatic stress disorder. In order to conduct "behavioral mapping" of the brain, they are also developing new techniques for creating reversible toxin-mediated inactivation of specific neuronal populations. |
| Representative Selected Recent Publications: |
- Nolan MF, Malleret G, Dudman JT, Buhl DL, Santoro B, Gibbs E, Vronskaya S, Buzsaki G, Siegelbaum SA, Kandel ER, and Morozov A:
A behavioral role for dendritic integration: HCN1 channels constrain spatial memory and plasticity at inputs to distal dendrites of CA1 pyramidal neurons
Cell., 2004 Nov 24;119(5):719-32.
- Morozov A, Kellendonk C, Simpson E, Tronche F:
Using conditional mutagenesis to study the brain. Biol. Psychiatry, 2003 Dec 1; 54(11): 1125-33.
- Nolan MF, Malleret G, Lee KH, Gibbs E., Dudman JT, Santoro, B, Yin D, Thompson RF, Siegelbaum SA, Kandel ER and A Morozov:
The hyperpolarization-activated HCN1 channel is important for motor learning and neuronal integration by cerebellar Purkinje cells.
Cell., 2003, Nov 26; 115(5): 551-64.
- Alexei Morozov, Izabel Muzzio, Rusiko Bourtchouladze, Niels Van-Strien, Kyle Lapidus, DeQi Yin, Danny Winder, Page Adams, David Sweatt and Eric Kandel:
Rap1 couples camp signaling to a distinct pool of p42/44MAPK regulating excitability, synaptic plasticity, learning and memory.
Neuron., 2003, July; 39(2): 309-325.
- Stanislav S. Zakharenko, Steven A. Siegelbaum, Eric R. Kandel1, and Alexei Morozov:
Selective involvement of presynaptic BDNF in presynaptic but not postsynaptic forms of hippocampal CA3-CA1 LTP.
Neuron., 2003, Sep; 39(6): 975-990.
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