Abstract

Signal transduction via protein phosphorylation plays a critical role in learning and memory. In a prominent candidate mechanism for mammalian learning and memory, hippocampal long-term potentiation (LTP), a diverse set of protein kinases plays an important role. Thus, the cAMP-dependent protein kinase (PKA), calcium/phospholipid-dependent kinase (PKC), calcium/calmodulin-dependent protein kinase (CaMKII), and mitogen-activated protein kinase (MAP kinase) all are necessary for the induction of various phases of LTP. While great progress has been made in identifying the kinases involved in LTP, there are many gaps in our knowledge of how the protein kinases are regulated by NMDA receptor-dependent and independent processes during LTP. In addition, little is understood concerning the downstream targets of these kinases. To address this question, three specific aims are proposed:
Specific Aim 1, to investigate the regulation of phosphorylation of the Shal-type K+ channel Kv4.2 in LTP, Specific Aim 2, to investigate the biochemical mechanisms for the activation of MAP kinase during LTP and Specific Aim 3, to investigate the role of protein kinases in regulating CREB phosphorylation during LTP. These studies will provide insight into mechanisms involved in long-lasting changes in neuronal function in the mammalian CNS and should increase our understanding of the molecular basis of neuropsychiatric disorders.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH057014-07
Application #
6637588
Study Section
Special Emphasis Panel (ZRG1-IFCN-7 (01))
Program Officer
Asanuma, Chiiko
Project Start
1996-09-01
Project End
2005-02-28
Budget Start
2003-03-01
Budget End
2004-02-29
Support Year
7
Fiscal Year
2003
Total Cost
$305,068
Indirect Cost

  Institution

Name
Baylor College of Medicine
Department
Neurosciences
Type
Schools of Medicine
DUNS #
051113330
City
Houston
State
TX
Country
United States
Zip Code
77030

  Publications

Bales, Katie L; Ianov, Lara; Kennedy, Andrew J et al. (2018) Autosomal dominant retinitis pigmentosa rhodopsin mutant Q344X drives specific alterations in chromatin complex gene transcription. Mol Vis 24:153-164
Cambronero, Francis E; Liu, Dandan; Neal, Jacquelyn E et al. (2018) APOE genotype modifies the association between central arterial stiffening and cognition in older adults. Neurobiol Aging 67:120-127
Ianov, Lara; De Both, Matt; Chawla, Monica K et al. (2017) Hippocampal Transcriptomic Profiles: Subfield Vulnerability to Age and Cognitive Impairment. Front Aging Neurosci 9:383
Sweatt, J. David (2017) Layered-up regulation in the developing brain. Nature 551:448-449
Duke, Corey G; Kennedy, Andrew J; Gavin, Cristin F et al. (2017) Experience-dependent epigenomic reorganization in the hippocampus. Learn Mem 24:278-288
Kennedy, Andrew J; Rahn, Elizabeth J; Paulukaitis, Brynna S et al. (2016) Tcf4 Regulates Synaptic Plasticity, DNA Methylation, and Memory Function. Cell Rep 16:2666-2685
Heyward, Frankie D; Gilliam, Daniel; Coleman, Mark A et al. (2016) Obesity Weighs down Memory through a Mechanism Involving the Neuroepigenetic Dysregulation of Sirt1. J Neurosci 36:1324-35
Kennedy, Andrew J; Sweatt, J David (2016) Drugging the methylome: DNA methylation and memory. Crit Rev Biochem Mol Biol 51:185-94
Savell, Katherine E; Gallus, Nancy V N; Simon, Rhiana C et al. (2016) Extra-coding RNAs regulate neuronal DNA methylation dynamics. Nat Commun 7:12091
Sweatt, J David (2016) Dynamic DNA methylation controls glutamate receptor trafficking and synaptic scaling. J Neurochem 137:312-30

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