The long-range goal is to understand how animals process events in time and remember these events in order to provide a theoretical framework for understanding disorders of memory. The objective of the present application is to identify behavioral mechanisms by which rats discriminate what, where, and when. Attainment of this objective is important because of the prominence of impairments in the content of memory - memories of what, where, and when an event occurred - in Alzheimer's disease and other common forms of human memory pathology. The central hypothesis is that rats time intervals with respect to significant earlier events to discriminate what, where, and when. The PI will test the central hypothesis by accomplishing two specific aims: 1. To identify the revisit strategy used to discriminate what, where, and when. The working hypothesis is that rats solve the discrimination of what, where, and when by learning specific what-when contingencies. The working hypothesis will be tested by training rats to discriminate what, where, and when using two what-when contingencies (i.e., two contingencies that govern replenishment of two distinctive flavors). 2. To identify the temporal mechanisms used to discriminate what, where, and when. The working hypothesis is that rats time intervals between significant events (e.g., study and test phases) in the discrimination of what, where, and when. Consequently, standard psychophysical methods of investigating interval timing will be used to investigate the temporal mechanisms involved in the discrimination of what, where, and when. This hypothesis will be tested by (1) obtaining generalization gradients, (2) examining the scalar property of temporal variability, and (3) identifying temporal resetting mechanisms in the discrimination of what, where, and when. Deficits in episodic memory in humans are deficits in the memory of what, where, and when events occurred (i.e., the content of episodic memory). Therefore, investigating the discrimination of what, where, and when in animals holds enormous potential for understanding disorders of human memory. The health relatedness of the project includes identifying mechanisms that govern the discrimination of what, where, and when to understand disorders of memory. Basic research of this type provides the foundation for new insights into the nature and origins of mental and behavioral disorders, which may ultimately impact development of improved treatments in future research. Therefore, the proposed research will identify the behavioral mechanisms of the discrimination of what, where, and when in rats to facilitate our understanding of fundamental aspects of cognition that may become dysfunctional within mental disorders. Identification of such behavioral mechanisms is essential to facilitate future progress in understanding the basic neurobiology of the network of brain regions (including the hippocampus) that support normal cognitive function, with the ultimate goal of determining how abnormalities in these systems give rise to mental illness.

Public Health Relevance

The study of basic mechanisms that govern memory is an urgent public health need because disorders of memory, such as Alzheimer's disease and other common forms of human memory pathology, impose a significant socioeconomic burden on society. Deficits in the content of memory for what, where, and when events occurred are implicated in disorders of memory. Therefore, investigating the discrimination of what, where, and when in animals holds enormous potential for understanding the neurobiological bases of human memory disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH080052-04
Application #
7989119
Study Section
Biobehavioral Regulation, Learning and Ethology Study Section (BRLE)
Program Officer
Osborn, Bettina D
Project Start
2009-01-10
Project End
2012-11-30
Budget Start
2010-12-01
Budget End
2012-11-30
Support Year
4
Fiscal Year
2011
Total Cost
$190,575
Indirect Cost
Name
Indiana University Bloomington
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
006046700
City
Bloomington
State
IN
Country
United States
Zip Code
47401
Wilson, A George; Matell, Matthew S; Crystal, Jonathon D (2015) The influence of multiple temporal memories in the peak-interval procedure. Learn Behav 43:153-62
Crystal, Jonathon D; Alford, Wesley T (2014) Validation of a rodent model of source memory. Biol Lett 10:20140064
Wilson, A George; Pizzo, Matthew J; Crystal, Jonathon D (2013) Event-based prospective memory in the rat. Curr Biol 23:1089-93
Crystal, Jonathon D; Ketzenberger, J Aaron; Alford, Wesley T (2013) Practicing memory retrieval improves long-term retention in rats. Curr Biol 23:R708-9
Crystal, Jonathon D; Alford, Wesley T; Zhou, Wenyi et al. (2013) Source memory in the rat. Curr Biol 23:387-91
Crystal, Jonathon D (2013) Remembering the past and planning for the future in rats. Behav Processes 93:39-49
Zhou, Wenyi; Hohmann, Andrea G; Crystal, Jonathon D (2012) Rats answer an unexpected question after incidental encoding. Curr Biol 22:1149-53
Wilson, A George; Crystal, Jonathon D (2012) Prospective memory in the rat. Anim Cogn 15:349-58
Crystal, Jonathon D (2012) Prospective cognition in rats. Learn Motiv 43:181-191
Foote, Allison L; Crystal, Jonathon D (2012) ""Play it Again"": a new method for testing metacognition in animals. Anim Cogn 15:187-99

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