Despite decades of research on the significance of local translation in memory storage, very little is known about the identity of the different RNAs translated at specific synapses, the temporal window of their stoichiometric changes, and how they are utilized at synapses in any system. RNAs are actively transported to synapses as ribo-nucleoprotein complexes by molecular motors. There are more than 40 different RNA binding proteins identified in a mouse brain. We have developed a genomics approach to identify all RNAs transported to synapses by focusing on the actively transported ribo-nucleoprotein complexes. This strategy involves isolation and characterization of immunoprecipitated molecular motor complexes from the tissue of interest. We propose to identify and characterize coding and noncoding RNAs transported to the hippocampal and prefrontal cortex (PFC) synapses by isolation and characterization of protein complexes transported by kinesin, a microtubule dependent molecular motor that moves from the cell-body to distal neuronal processes. The long-term goal of this project is to identify and characterize molecular substrates of synaptic translation and their temporal regulation during initiation and persistence of long-term memory storage at the hippocampal and PFC synapses, the two critical brain regions involved in storage and consolidation of long-term memories.

Public Health Relevance

Focusing on the hippocampal and prefrontal cortex neurons of the mouse brain, this project will identify all the coding and noncoding RNAs that are actively transported to synapses. This data will be used to identify and characterize signaling networks at the synapse that are regulated by local translation during storage and consolidation of long-term memories.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21MH096258-02
Application #
8485685
Study Section
Molecular Neurogenetics Study Section (MNG)
Program Officer
Beckel-Mitchener, Andrea C
Project Start
2012-06-11
Project End
2014-05-31
Budget Start
2013-06-01
Budget End
2014-05-31
Support Year
2
Fiscal Year
2013
Total Cost
$223,680
Indirect Cost
$70,560
Name
Scripps Florida
Department
Type
DUNS #
148230662
City
Jupiter
State
FL
Country
United States
Zip Code
33458
Liu, Xin-An; Kadakkuzha, Beena; Pascal, Bruce et al. (2014) New approach to capture and characterize synaptic proteome. Proc Natl Acad Sci U S A 111:16154-9
Kadakkuzha, Beena M; Puthanveettil, Sathyanarayanan V (2013) Genomics and proteomics in solving brain complexity. Mol Biosyst 9:1807-21