Mounting evidence indicates that adult mental health status is strongly influenced by the quality of early life care. Abuse, neglect, isolation, and poverty have all been associated with poorer cognitive abilities in adulthood and aging. Moreover, the proportion of the US population that is elderly currently grows at a rapid pace and will reach 20% of the total population by 2030. This translates into a troubling burden on the US health care system to treat aging-related cognitive decline. However, this problem may be avoided if rapid action is taken to identify at-risk individuals and create prophylactic interventions. A better understanding of individual risk for memory impairment in adulthood and aging can be gained by knowing how neural systems that regulate memory are assembled during postnatal development. The proposed project is geared toward understanding the episodic and prospective memory impairments that are associated with human aging by focusing on the postnatal age in rats when these memory systems are undergoing their final maturation, the end of the third postnatal week. This age in rats parallels the final maturation of episodic memory in humans, which begins at about three years after birth. This lifespan-based research design employ assays at the molecular, cellular, pharmacological, systems, and behavioral levels. More specifically, the proposed experiments examine changes in the molecular structure of fast-acting synaptic glutamate receptors (AMPA receptors) at hippocampal synapses and relationships to alterations in neuronal function and spatial navigation ability. This multidisciplinary project should uncover early biomarkers for impending memory impairment, which will aid in understanding the considerable variability in episodic and prospective memory abilities in adulthood and aging. Additionally, findings will improve the design of prophylactic measures for memory maintenance and promote more effective treatments for memory impairments in aging.

Public Health Relevance

The elderly population in the US continues to grow at a staggering rate meaning there are more and more individuals suffering cognitive impairment. As such, for individual, social, and economic reasons, it is critical to understand how memory systems are built and what makes them susceptible to decline in aging. Our research promotes the discovery of earlier markers of impending memory loss and the development of effective interventions.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Academic Research Enhancement Awards (AREA) (R15)
Project #
1R15AG045820-01A1
Application #
8687392
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Wagster, Molly V
Project Start
2014-05-15
Project End
2017-04-30
Budget Start
2014-05-15
Budget End
2017-04-30
Support Year
1
Fiscal Year
2014
Total Cost
Indirect Cost
Name
George Mason University
Department
Type
Organized Research Units
DUNS #
City
Fairfax
State
VA
Country
United States
Zip Code
22030
Dumas, Theodore C; Uttaro, Michael R; Barriga, Carolina et al. (2018) Removal of area CA3 from hippocampal slices induces postsynaptic plasticity at Schaffer collateral synapses that normalizes CA1 pyramidal cell discharge. Neurosci Lett 678:55-61
Valibeigi, Nazanin; McHail, Daniel G; Kimball, Carmen L et al. (2018) A Modified Barnes Maze for Juvenile Rats. Bio Protoc 8:
McHail, Daniel G; Valibeigi, Nazanin; Dumas, Theodore C (2018) A Barnes maze for juvenile rats delineates the emergence of spatial navigation ability. Learn Mem 25:138-146
Sanders, Erin M; Nyarko-Odoom, Akua O; Zhao, Kevin et al. (2018) Separate functional properties of NMDARs regulate distinct aspects of spatial cognition. Learn Mem 25:264-272
Stoneham, Emily T; McHail, Daniel G; Boggs, Katelyn N et al. (2017) Functional perturbation of forebrain principal neurons reveals differential effects in novel and well-learned tasks. Brain Res 1671:1-13
Gardner, Robert S; Suarez, Daniel F; Robinson-Burton, Nadira K et al. (2016) Differential Arc expression in the hippocampus and striatum during the transition from attentive to automatic navigation on a plus maze. Neurobiol Learn Mem 131:36-45
McHail, Daniel G; Dumas, Theodore C (2015) Multiple forms of metaplasticity at a single hippocampal synapse during late postnatal development. Dev Cogn Neurosci 12:145-54
Albani, Sarah H; Andrawis, Marina M; Abella, Rio Jeane H et al. (2015) Behavior in the elevated plus maze is differentially affected by testing conditions in rats under and over three weeks of age. Front Behav Neurosci 9:31
Albani, Sarah H; McHail, Daniel G; Dumas, Theodore C (2014) Developmental studies of the hippocampus and hippocampal-dependent behaviors: insights from interdisciplinary studies and tips for new investigators. Neurosci Biobehav Rev 43:183-90
Blair, Margaret G; Nguyen, Nhu N-Q; Albani, Sarah H et al. (2013) Developmental changes in structural and functional properties of hippocampal AMPARs parallels the emergence of deliberative spatial navigation in juvenile rats. J Neurosci 33:12218-28