A critical issue for both neuroscientists and society at large concerns the relative roles of genetics and environment in the postnatal development of the human brain. Environmental stimuli are wide ranging, from the detrimental (chemical toxicants, for example) to the beneficial (a mother's instructions), but all have the potential to influence the developmental program of a child as directed by its genome. The research done in the Synaptic and Developmental Plasticity Group focuses on determining 1) how the connections in the brain (synapses) change on a long-term basis in response to neuronal activity, 2) how synaptic plasticity during early postnatal development is different from plasticity in the adult, and 3) how experience shapes brain circuitry through synapse elimination during development. Though only in operation for six months, we have made significant progress in developing some of the methodologies that will be used in achieving the first of the aforementioned projects. We believe that long-term changes in synaptic efficacy require expression of new RNA and toward that end, we have focused on the regulation of gene expression by neuronal action potentials. To measure enzyme activity modulated by action potentials, we have developed a method for isolating nuclei from small amounts of brain tissue, which had first been electrically stimulated in vitro. We have also perfected a method of measuring the activation of up to 96 transcription factors using a protein/DNA array. These techniques will allow the examination of transcriptional regulation by neuronal activity and will lead to an understanding of how genes required for plasticity are regulated. Together with the other goals listed above, these studies should bring us a better appreciation of how environmental factors play a role in brain development so that we may begin to address the associated problems of brain disease caused by toxicant exposure.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Intramural Research (Z01)
Project #
1Z01ES100221-01
Application #
6673277
Study Section
(LT)
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2002
Total Cost
Indirect Cost
Name
U.S. National Inst of Environ Hlth Scis
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Tyssowski, Kelsey M; DeStefino, Nicholas R; Cho, Jin-Hyung et al. (2018) Different Neuronal Activity Patterns Induce Different Gene Expression Programs. Neuron 98:530-546.e11
Alexander, Georgia M; Brown, Logan Y; Farris, Shannon et al. (2018) CA2 neuronal activity controls hippocampal low gamma and ripple oscillations. Elife 7:
Henson, Maile A; Tucker, Charles J; Zhao, Meilan et al. (2017) Long-term depression-associated signaling is required for an in vitro model of NMDA receptor-dependent synapse pruning. Neurobiol Learn Mem 138:39-53
Marron Fernandez de Velasco, Ezequiel; Zhang, Lei; N Vo, Baovi et al. (2017) GIRK2 splice variants and neuronal G protein-gated K+ channels: implications for channel function and behavior. Sci Rep 7:1639
Carstens, Kelly E; Phillips, Mary L; Pozzo-Miller, Lucas et al. (2016) Perineuronal Nets Suppress Plasticity of Excitatory Synapses on CA2 Pyramidal Neurons. J Neurosci 36:6312-20
Alexander, Georgia M; Farris, Shannon; Pirone, Jason R et al. (2016) Social and novel contexts modify hippocampal CA2 representations of space. Nat Commun 7:10300
Dudek, Serena M; Alexander, Georgia M; Farris, Shannon (2016) Rediscovering area CA2: unique properties and functions. Nat Rev Neurosci 17:89-102
Sciolino, Natale R; Plummer, Nicholas W; Chen, Yu-Wei et al. (2016) Recombinase-Dependent Mouse Lines for Chemogenetic Activation of Genetically Defined Cell Types. Cell Rep 15:2563-73
Pagani, J H; Zhao, M; Cui, Z et al. (2015) Role of the vasopressin 1b receptor in rodent aggressive behavior and synaptic plasticity in hippocampal area CA2. Mol Psychiatry 20:490-9
Evans, Paul R; Dudek, Serena M; Hepler, John R (2015) Regulator of G Protein Signaling 14: A Molecular Brake on Synaptic Plasticity Linked to Learning and Memory. Prog Mol Biol Transl Sci 133:169-206

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