This proposal is aimed at understanding the neural mechanisms of learning and memory. An extensive literature has documented the role of the hippocampus and the posterior cingulate cortex in memory functions. Damage to these brain regions has been linked to the memory impairments seen in Alzheimer's disease, age-related memory decline and various human amnesic syndromes and learning disabilities. Understanding how these systems work is crucial for the development of treatment strategies for patients with these conditions. The memory role of the hippocampus has been well documented and, although it has not been studied as extensively, the posterior cingulate cortex is also known to play a critical role in learning and memory. However, the precise contribution of each of these brain regions to the learning process remains unclear. Recent findings suggest that these two closely interconnected structures form a functional circuit which mediates contextual learning, but that each region makes a distinct contribution to the learning process. Findings of context-specific neuronal firing patterns suggest that the hippocampus generates a neural representation of the context. In contrast, neuronal responses to discrete cues suggest that the posterior cingulate cortex encodes behaviorally significant cues, including those cues that uniquely identify the context. These two regions function cooperatively to mediate contextual learning and memory. However, the relative contribution of each brain region should depend on the degree to which the task at hand requires the processing of contextual information or discrete cues. To examine this, rats will be trained on various contextual learning tasks which have differing cue- and context processing requirements. Neuronal activity will be recorded in both the hippocampus and posterior cingulate cortex throughout learning. Temporary neurochemical brain lesions will be used to disable each brain region, so that it will be possible to identify the specific contribution of each brain region to learning and to determine how the loss of one region disrupts processing in the other region. By monitoring the changes in neuronal responses as subjects learn and the effects of temporary damage to the circuit, it will be possible to determine what kinds of memory related information is processed in each brain region and how their interactions yield context-specific memories.

Public Health Relevance

This research is relevant to public health because it investigates the learning and memory systems of the brain, particularly the hippocampus and posterior cingulate cortex. Damage to these brain regions has been linked to the memory impairments seen in Alzheimer's disease, age-related memory decline and various other amnesic syndromes and learning disabilities. Understanding how these systems work is crucial for the development of treatment strategies for patients with these conditions.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH083809-05
Application #
8598814
Study Section
Neurobiology of Learning and Memory Study Section (LAM)
Program Officer
Osborn, Bettina D
Project Start
2009-12-02
Project End
2014-11-30
Budget Start
2013-12-01
Budget End
2014-11-30
Support Year
5
Fiscal Year
2014
Total Cost
$283,338
Indirect Cost
$105,138
Name
Cornell University
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
872612445
City
Ithaca
State
NY
Country
United States
Zip Code
14850
Smith, David M; Bulkin, David A (2014) The form and function of hippocampal context representations. Neurosci Biobehav Rev 40:52-61
Wu, Jade Q; Peters, Greg J; Rittner, Pedro et al. (2014) The hippocampus, medial prefrontal cortex, and selective memory retrieval: evidence from a rodent model of the retrieval-induced forgetting effect. Hippocampus 24:1070-80
Peters, Gregory J; David, Christopher N; Marcus, Madison D et al. (2013) The medial prefrontal cortex is critical for memory retrieval and resolving interference. Learn Mem 20:201-9
Smith, David M; Barredo, Jennifer; Mizumori, Sheri J Y (2012) Complimentary roles of the hippocampus and retrosplenial cortex in behavioral context discrimination. Hippocampus 22:1121-33
Butterly, Dan A; Petroccione, Maurice A; Smith, David M (2012) Hippocampal context processing is critical for interference free recall of odor memories in rats. Hippocampus 22:906-13
Gill, Patrick R; Mizumori, Sheri J Y; Smith, David M (2011) Hippocampal episode fields develop with learning. Hippocampus 21:1240-9