A major goal of cognitive neuroscience is to understand behavior and mental processes in terms of the physiological properties of neural circuits. Spatial learning is a prominent paradigm for studying these issues. Mammalian brains encode a cognitive map of the environment, which is used to remember and navigate to important locations. Place cells of the hippocampus, which fire in restricted locations in space, are thought to constitute this cognitive map. The goal of this research program is to understand how place cells and neurons in related areas interact to generate the spatially specific firing of these neurons. The role of hippocampus in learning and memory has been modeled as an associative network with two important properties: pattern completion, the ability to retrieve a stored pattern from degraded input, and pattern separation, the ability to make stored representations of similar inputs more dissimilar. Theoretical and experimental studies hypothesize that (1) the dentate gyrus performs pattern separation; (2) CA3 performs pattern completion; (3) CA1 compares the CA3 output with entorhinal cortex; and (4) the subiculum encodes a universal map for path integration. Powerful, new multi-electrode technology will be used to record dozens of neurons simultaneously for these brain areas to test these hypotheses. These recordings will allow within-animal comparisons of the changes induced in the spatial maps encoded by each area as a result of experimental manipulations. It is hypothesized that (1) dentate gyrus will """"""""remap"""""""" an environment in a graded fashion; (2) CA3 will be unaffected by small environmental changes but will form new representations for large changes; (3) CA1 will also be unaffected by small changes, but will tend to remap large changes only partially; and (4) subiculum will be unaffected by these manipulations. The devastating neurological effects of such diseases as Alzheimer's Disease and epilepsy are intimately tied to dysfunctions of the hippocampus and related brain areas. These experiments will generated fundamental insights into the neural interactions between these brain areas that underlie learning and memory, as well as insights into how these mechanisms go awry in these debilitating diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS039456-02
Application #
6330615
Study Section
Special Emphasis Panel (ZRG1-IFCN-7 (01))
Program Officer
Chen, Daofen
Project Start
1999-12-01
Project End
2003-11-30
Budget Start
2000-12-01
Budget End
2001-11-30
Support Year
2
Fiscal Year
2001
Total Cost
$167,425
Indirect Cost
Name
University of Texas Health Science Center Houston
Department
Neurosciences
Type
Schools of Medicine
DUNS #
City
Houston
State
TX
Country
United States
Zip Code
77225
Wang, Cheng; Chen, Xiaojing; Lee, Heekyung et al. (2018) Egocentric coding of external items in the lateral entorhinal cortex. Science 362:945-949
Savelli, Francesco; Luck, J D; Knierim, James J (2017) Framing of grid cells within and beyond navigation boundaries. Elife 6:
Connor, Charles E; Knierim, James J (2017) Integration of objects and space in perception and memory. Nat Neurosci 20:1493-1503
Knierim, James J; Neunuebel, Joshua P (2016) Tracking the flow of hippocampal computation: Pattern separation, pattern completion, and attractor dynamics. Neurobiol Learn Mem 129:38-49
Lee, Heekyung; Wang, Cheng; Deshmukh, Sachin S et al. (2015) Neural Population Evidence of Functional Heterogeneity along the CA3 Transverse Axis: Pattern Completion versus Pattern Separation. Neuron 87:1093-105
Knierim, James J (2015) From the GPS to HM: Place cells, grid cells, and memory. Hippocampus 25:719-25
Knierim, James J; Neunuebel, Joshua P; Deshmukh, Sachin S (2014) Functional correlates of the lateral and medial entorhinal cortex: objects, path integration and local-global reference frames. Philos Trans R Soc Lond B Biol Sci 369:20130369
Neunuebel, Joshua P; Knierim, James J (2014) CA3 retrieves coherent representations from degraded input: direct evidence for CA3 pattern completion and dentate gyrus pattern separation. Neuron 81:416-27
Monaco, Joseph D; Rao, Geeta; Roth, Eric D et al. (2014) Attentive scanning behavior drives one-trial potentiation of hippocampal place fields. Nat Neurosci 17:725-31
Deshmukh, Sachin S; Knierim, James J (2013) Influence of local objects on hippocampal representations: Landmark vectors and memory. Hippocampus 23:253-67

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