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.
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.
|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|
|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|
|Sill, Orriana C; Smith, David M (2012) A comparison of the effects of temporary hippocampal lesions on single and dual context versions of the olfactory sequence memory task. Behav Neurosci 126:588-92|
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