Abstract

There is very little known about the mechanisms responsible for the very long-term storage of information in the neocortex. Recent studies from our laboratory suggest that besides its role in the hippocampus, the alpha calcium calmodulin kinase II (aCaMKII) is critical for cortical plasticity and for remote memory consolidation in neocortical networks. Here, we propose to use a combination of behavioral neuroscience tools, in vivo time-lapse 2 photon laser scanning microscopy (2P LSM), inducible and region-specific molecular approaches to unravel the role of aCaMKII in cortical memory storage.
The specific aims of this proposal are:
Specific Aim #1 - To determine the function of the anterior cingulate and retrosplinial cortex in remote memory in mice. Our preliminary results indicate that these two structures are required for remote memory. Now we would like to define their roles in this poorly understood memory phase.
Specific Aim #2 - To determine the role of aCaMKII in anterior cingulate and retrosplinial cortex in remote memory. Our previoous results demonstrated a role for this kinase in remote memory. These studies will be critical to determine where this kinase is needed and how it modulates remote memory.
Specific Aim #3 - To use time lapse in vivo 2P LSM to uncover the role of aCaMKII in synaptic restructuring in anterior cingulate and retrosplinial cortex, (close collaboration with Dr. Joshua Trachtenberg, a co-Pi in this proposal and a pioneer in the ground breaking 2P LSM). There is extensive evidence that CAMKII modulates synaaptic retructuring. Now, we would to characterize these events in vivo and test their impact on remote memory. The experiments proposed here represent some of the first steps in the study of the molecular and cellular mechanisms underlying the storage of memories in cortical networks. Besides their impact on the understanding of remote memory, the results from these studies will be important to understand cognitive disorders associated with age-related cognitive decline and progressive neurodegenerative disorders such as Alzheimer's disease, since these conditions affect the regions and the memory processes that we propose to study.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37AG013622-19
Application #
8828040
Study Section
Special Emphasis Panel (NSS)
Program Officer
Wagster, Molly V
Project Start
1995-07-25
Project End
2017-03-31
Budget Start
2015-04-01
Budget End
2016-03-31
Support Year
19
Fiscal Year
2015
Total Cost
$525,451
Indirect Cost
$184,249

  Institution

Name
University of California Los Angeles
Department
Neurosciences
Type
Schools of Medicine
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095

  Publications

Cai, Denise J; Aharoni, Daniel; Shuman, Tristan et al. (2016) A shared neural ensemble links distinct contextual memories encoded close in time. Nature 534:115-8
Kastellakis, George; Silva, Alcino J; Poirazi, Panayiota (2016) Linking Memories across Time via Neuronal and Dendritic Overlaps in Model Neurons with Active Dendrites. Cell Rep 17:1491-1504
Kastellakis, George; Cai, Denise J; Mednick, Sara C et al. (2015) Synaptic clustering within dendrites: an emerging theory of memory formation. Prog Neurobiol 126:19-35
Sano, Yoshitake; Shobe, Justin L; Zhou, Miou et al. (2014) CREB regulates memory allocation in the insular cortex. Curr Biol 24:2833-7
Rogerson, Thomas; Cai, Denise J; Frank, Adam et al. (2014) Synaptic tagging during memory allocation. Nat Rev Neurosci 15:157-69
Czajkowski, Rafa?; Jayaprakash, Balaji; Wiltgen, Brian et al. (2014) Encoding and storage of spatial information in the retrosplenial cortex. Proc Natl Acad Sci U S A 111:8661-6
Achterberg, Katharina G; Buitendijk, Gabriëlle H S; Kool, Martijn J et al. (2014) Temporal and region-specific requirements of ?CaMKII in spatial and contextual learning. J Neurosci 34:11180-7
Zhou, Miou; Li, Weidong; Huang, Shan et al. (2013) mTOR Inhibition ameliorates cognitive and affective deficits caused by Disc1 knockdown in adult-born dentate granule neurons. Neuron 77:647-54
Cho, Jeiwon; Bhatt, Rushi; Elgersma, Ype et al. (2012) ?-Calcium calmodulin kinase II modulates the temporal structure of hippocampal bursting patterns. PLoS One 7:e31649
Ehninger, D; Sano, Y; de Vries, P J et al. (2012) Gestational immune activation and Tsc2 haploinsufficiency cooperate to disrupt fetal survival and may perturb social behavior in adult mice. Mol Psychiatry 17:62-70

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