This project is aimed at understanding the neural mechanisms of learning and memory. An extensive literature has documented the role of the hippocampus, retrosplenial cingulate cortex and anterior thalamus in memory functions. Damage to these brain regions is a primary cause of the memory impairments seen in Alzheimer's disease, age-related memory decline, and various human amnesic syndromes and learning disabilities. Abnormalities in these structures have also been implicated in depression, anxiety and schizophrenia. Understanding the function of these systems 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 they have not been studied as extensively, the retrosplenial cortex and anterior thalamus are 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 closely interconnected structures form a functional circuit which mediates spatial and contextual memory. The proposed experiments are focused on understanding how memory-related information is represented by neurons in the retrosplenial cortex, and how interactions of the retrosplenial cortex, hippocampus and anterior thalamus support memory functions. In order to investigate this, neuronal activity will be recorded in these brain regions as rats perform various spatial and contextual memory tasks. Optogenetic, chemogenetic and neurochemical methods will be used to suppress neuronal activity in various components of this circuit in order to assess their contributions to functioning in the broader memory circuit. By monitoring neuronal responses as subjects learn and the effects of temporary inactivation within the circuit, it will be possible to determine how memory related information is processed and how memory may fail when damage occurs within the circuit.

Public Health Relevance

This research is relevant to public health because it investigates the learning and memory systems of the brain, particularly the hippocampus, retrosplenial cortex, and anterior thalamus. Damage to each of these brain regions has been linked to the memory impairments seen in Alzheimer's disease, age-related memory decline and various other amnesic syndromes, as well as psychopathology including depression, anxiety and schizophrenia. Understanding how these systems work is crucial for the development of treatment strategies for patients with these conditions.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
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Study Section
Neurobiology of Learning and Memory Study Section (LAM)
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Buhring, Bettina D
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Cornell University
Schools of Arts and Sciences
United States
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Smith, David M; Miller, Adam M P; Vedder, Lindsey C (2018) The retrosplenial cortical role in encoding behaviorally significant cues. Behav Neurosci 132:356-365
Vedder, Lindsey C; Miller, Adam M P; Harrison, Marc B et al. (2017) Retrosplenial Cortical Neurons Encode Navigational Cues, Trajectories and Reward Locations During Goal Directed Navigation. Cereb Cortex 27:3713-3723
Bulkin, David A; Law, L Matthew; Smith, David M (2016) Placing memories in context: Hippocampal representations promote retrieval of appropriate memories. Hippocampus 26:958-71
Law, L Matthew; Bulkin, David A; Smith, David M (2016) Slow stabilization of concurrently acquired hippocampal context representations. Hippocampus 26:1560-1569
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
Miller, Adam M P; Vedder, Lindsey C; Law, L Matthew et al. (2014) Cues, context, and long-term memory: the role of the retrosplenial cortex in spatial cognition. Front Hum Neurosci 8:586
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
Law, L Matthew; Smith, David M (2012) The anterior thalamus is critical for overcoming interference in a context-dependent odor discrimination task. Behav Neurosci 126:710-9

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