Numerous studies have demonstrated the importance of CREB in memory consolidation. However, recent findings suggest that CREB also plays a key role in memory allocation. Increasing the levels of CREB increases the probability that a given neuron in the amygdala will be recruited into a memory trace, while decreasing the levels of CREB has the opposite effect. Previous results also suggest that CREB affects memory allocation by altering neuronal excitability, whereby high levels of CREB increases the intrinsic excitability of neurons in the amygdala which biases these cells towards being included in the memory trace. While there is convincing evidence that CREB and neuronal excitability are important for memory allocation in the amygdala, it is unclear whether these principles generalize to other brain regions important for memory, such as the hippocampus. I propose to directly test this hypothesis by manipulating a subpopulation of CA1 neurons with viral CREB to see if the representation is biased towards those neurons with increased CREB. Additionally, I will examine the temporal dynamics of CREB activation and neuronal excitability in CA1 following acquisition of a context memory using Western blot analysis and whole cell patch recording, respectively. Lastly, I will examine the co-allocation of two memories with transgenic TetTag mice, which can label activated neurons at 2 different time points. My prediction is that if CREB biases memory allocation, then increased CREB activation induced by one hippocampus-dependent memory should bias the allocation of a second memory to many of the same neurons recruited to store the first memory. Our previous studies in the lateral amygdala pioneered the field of memory allocation. While this field has been very exciting, it has been exclusively limited to the amygdala and for this field to move forward, it is essential that we can generalize our findings to other brains structures and memory types. The results from these proposed studies will give us a better idea of how memory allocation processes affect the integration and storage of information. With this knowledge, we can better develop targeted treatments for memory disorders, including Alzheimer?s disease, as we already know there is aberrant CREB-mediated gene regulation in this population.

Public Health Relevance

Alzheimer's disease (AD) is the most common form of dementia in the aging population and memory impairment is the principle defining feature. There is strong evidence that these patients have an aberrant regulation of CREB in the brain, which could be related to the memory loss. The results from these proposed studies will give us a better idea of how CREB affects the integration and storage of information. With this knowledge, we can better develop targeted treatments for memory disorders, including Alzheimer's disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32MH097413-02
Application #
8514400
Study Section
Special Emphasis Panel (ZRG1-F02A-J (20))
Program Officer
Li, Ingrid Y
Project Start
2012-06-01
Project End
2014-05-31
Budget Start
2013-06-01
Budget End
2014-05-31
Support Year
2
Fiscal Year
2013
Total Cost
$53,942
Indirect Cost
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
Rogerson, Thomas; Cai, Denise J; Frank, Adam et al. (2014) Synaptic tagging during memory allocation. Nat Rev Neurosci 15:157-69