The long-range goal is to understand how animals process and remember events in time and develop a neuro- anatomically guided theoretical framework for understanding memory disorders. The objective of the present exploratory R21 application is to begin to apply an animal model of prospective memory in rats to aging and identify its basic underlying cognitive mechanisms. The central hypothesis is that activation of prospective memory produces a selective deficit in performance in an ongoing task when anticipation of a future event is greatest. Our preliminary studies, which show an impairment in performance in an ongoing task near the time of an anticipated future event in adult rats (but not at other times), support this hypothesis. The working hypothesis is that deficits in prospective memory with aging will translate into selective sparing of performance in an ongoing task. Because anticipating a future event produces a deleterious side effect on ongoing activity, a decline in prospective memory is expected to attenuate the deleterious side effect (i.e., produce a relative sparing in the ability to carry out ongoing tasks). The Principal Investigator will testthe central hypothesis by accomplishing two specific aims: (1) To develop a rodent model of age-related decline in prospective memory. We will test the working hypothesis that a decline in prospective memory can be measured by sparing of ongoing performance in our prospective-memory task using cross sectional and longitudinal designs. We will also test the hypothesis that voluntary exercise produces protective effects on prospective memory in a longitudinal study. (2) To identify basic cognitive mechanisms in prospective memory. We will test the working hypothesis that adult rats anticipate a specific time in the future, temporarily disengage from a future plan, and deploy a learned plan in a novel context. Health relatedness of the project: Identifying mechanisms that govern prospective memory holds enormous potential to significantly benefit society by providing insights into deficits in memory associated with aging, mild cognitive impairment, Alzheimer's disease, brain injuries, amnesia, or other human memory pathologies. Identifying the basic cognitive mechanisms of prospective memory will enable future research to identify which underlying processes are protected or impaired during normal aging in rodents;this knowledge may ultimately be used to exploit naturally occurring mechanisms that may protect against age-related cognitive impairments. Understanding and exploiting protective effects on cognition may ultimately yield novel therapeutic approaches to age-related declines in cognition. Identifying mechanisms that govern prospective memory is necessary if we are to improve our understanding of the neural substrates underlying prospective memory and foster development of treatments for human memory disorders. Indeed, improving memory is an important objective for therapies of Alzheimer's disease and age-related cognitive decline. Ultimately, a better understanding of prospective memory offers the potential to develop targeted pharmacological and molecular treatments for cognitive decline that afflict normal and disordered aging.
Deficits in prospective memory are implicated in disorders of memory, which impose a significant socioeconomic burden on society. Thus, the study of normal and impaired prospective memory in aging is an urgent public health need. A better understanding of prospective memory impairments may ultimately (1) facilitate understanding the neurobiological bases of human memory disorders, (2) improve translational potential when testing new therapies with animals, and (3) reduce both escalating healthcare and long-term care costs and unnecessary suffering in patients and their families.
|Panoz-Brown, Danielle; Iyer, Vishakh; Carey, Lawrence M et al. (2018) Replay of Episodic Memories in the Rat. Curr Biol 28:1628-1634.e7|
|Smith, Alexandra E; Slivicki, Richard A; Hohmann, Andrea G et al. (2017) The chemotherapeutic agent paclitaxel selectively impairs learning while sparing source memory and spatial memory. Behav Brain Res 320:48-57|
|Panoz-Brown, Danielle; Carey, Lawrence M; Smith, Alexandra E et al. (2017) The chemotherapeutic agent paclitaxel selectively impairs reversal learning while sparing prior learning, new learning and episodic memory. Neurobiol Learn Mem 144:259-270|
|Smith, Alexandra E; Dalecki, Stefan J; Crystal, Jonathon D (2017) A test of the reward-value hypothesis. Anim Cogn 20:215-220|
|Crystal, Jonathon D (2016) Animal models of source memory. J Exp Anal Behav 105:56-67|
|Bratch, Alexander; Kann, Spencer; Cain, Joshua A et al. (2016) Working Memory Systems in the Rat. Curr Biol 26:351-5|
|Panoz-Brown, Danielle; Corbin, Hannah E; Dalecki, Stefan J et al. (2016) Rats Remember Items in Context Using Episodic Memory. Curr Biol 26:2821-2826|
|Smith, Alexandra E; Xu, Zhili; Lai, Yvonne Y et al. (2016) Source memory in rats is impaired by an NMDA receptor antagonist but not by PSD95-nNOS protein-protein interaction inhibitors. Behav Brain Res 305:23-9|
|Crystal, Jonathon D; Wilson, A George (2015) Prospective memory: a comparative perspective. Behav Processes 112:88-99|
|Crystal, Jonathon D; Smith, Alexandra E (2014) Binding of episodic memories in the rat. Curr Biol 24:2957-61|
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