The hippocampus is critically involved in flexible learning tasks, particularly in spatial navigation, reversal, and episodic-memory tasks and tasks that require planning and decision-making. In tasks with a spatial component, hippocampal cells show a strong spatial firing correlate (termed """"""""place fields""""""""). Because it is possible to record large neural ensembles from hippocampus, and because the set of place fields generally cover the entire environment, it is possible to reconstruct location from hippocampal neural ensembles. In spatial decision tasks, non-spatial information (episodic memory, decisions to be made, etc.) is projected onto the spatial domain. This means that the spatial tuning of place cells provides leverage with which to examine the dynamics of hippocampal representations on decision tasks. Using new reconstruction methods that enable the interpretation of representation of spatial location from neural ensembles at very fast (e.g. tens of ms) timescales, we have recently observed a reliable, repeatable phenomenon whenever rats paused at a decision point on a maze: During most behaviors, location reconstructed from the ensemble was an accurate representation of the rat's location within the maze. However, at decision points, the reconstructed location swept ahead of the rat, first down one potential path, and then down the other. After alternating back and forth for 500- 1000 ms, the representation returned to the location of the animal and the rat began running again. These non-local reconstructions reliably stretched forward of the animal rather than behind the animal. Our working hypothesis is that this phenomenon reflects a choice-consideration, path-, or goal-planning process. The objective of this proposal is to test this hypothesis and further our understanding of the mechanisms underlying these observations. Our plan of attack is to record neural ensembles in a cued-choice task and to determine the behavioral situations in which these phenomena occur. We will identify the location of the rat when these phenomena occur (e.g. does this only occur at choices?) and the locations which get reconstructed to (e.g. does it sweep all the way to the goal?). We will then characterize the hippocampal contribution to the phenomena through detailed comparison with afferent structures and a detailed analysis of hippocampal local field potentials, interneuron and pyramidal cell firing patterns, and the interaction between them. The work proposed here will increase our understanding of the role of the hippocampus in spatial navigation, episodic memory, and decision-making.

Public Health Relevance

Using novel analysis techniques applied to neural ensemble recordings, we have recently observed that hippocampal ensembles transiently encode the available choices when rats pause at decision-points. This objective of this proposal is to understand the mechanisms underlying this novel phenomenon, which may reflect a choice-consideration process. Understanding the mechanisms of the normal decision-making process will have implications for patients in which that process has broken down such as in anxiety disorders or other cognitive disorders such as Alzheimer's disease and Schizophrenia.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH080318-05
Application #
8267715
Study Section
Neurobiology of Learning and Memory Study Section (LAM)
Program Officer
Osborn, Bettina D
Project Start
2008-06-01
Project End
2014-05-31
Budget Start
2012-06-01
Budget End
2014-05-31
Support Year
5
Fiscal Year
2012
Total Cost
$269,082
Indirect Cost
$90,882
Name
University of Minnesota Twin Cities
Department
Neurosciences
Type
Schools of Medicine
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
Amemiya, Seiichiro; Redish, A David (2018) Hippocampal Theta-Gamma Coupling Reflects State-Dependent Information Processing in Decision Making. Cell Rep 22:3328-3338
Sweis, Brian M; Abram, Samantha V; Schmidt, Brandy J et al. (2018) Sensitivity to ""sunk costs"" in mice, rats, and humans. Science 361:178-181
Sweis, Brian M; Larson, Erin B; Redish, A David et al. (2018) Altering gain of the infralimbic-to-accumbens shell circuit alters economically dissociable decision-making algorithms. Proc Natl Acad Sci U S A 115:E6347-E6355
Sweis, Brian M; Redish, A David; Thomas, Mark J (2018) Prolonged abstinence from cocaine or morphine disrupts separable valuations during decision conflict. Nat Commun 9:2521
Lisman, John; Buzsáki, György; Eichenbaum, Howard et al. (2017) Viewpoints: how the hippocampus contributes to memory, navigation and cognition. Nat Neurosci 20:1434-1447
Papale, Andrew E; Zielinski, Mark C; Frank, Loren M et al. (2016) Interplay between Hippocampal Sharp-Wave-Ripple Events and Vicarious Trial and Error Behaviors in Decision Making. Neuron 92:975-982
Amemiya, Seiichiro; Redish, A David (2016) Manipulating Decisiveness in Decision Making: Effects of Clonidine on Hippocampal Search Strategies. J Neurosci 36:814-27
Abram, Samantha V; Breton, Yannick-André; Schmidt, Brandy et al. (2016) The Web-Surf Task: A translational model of human decision-making. Cogn Affect Behav Neurosci 16:37-50
Redish, A David (2016) Vicarious trial and error. Nat Rev Neurosci 17:147-59
Carter, Evan C; Redish, A David (2016) Rats value time differently on equivalent foraging and delay-discounting tasks. J Exp Psychol Gen 145:1093-101

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