The hippocampal formation is essential for the storage of certain types of memories, including memories for facts and events in humans and memories for space in rodents. Understanding the role of the hippocampus in learning is a complex problem, in part because the hippocampus is not a single region but is instead made of up several areas, including the entorhinal cortex (EC), dentate gyrus (DG), CA3, CA1 and the subiculum, each of which may play a unique role in this process. In addition, learning is itself a complex phenomenon involving multiple behavioral and cognitive components. The challenge, then, is to go beyond the shorthand of discussing the hippocampus and learning and instead begin to examine the role of each area within the hippocampal circuit in the learning and representation of complex tasks. For spatial tasks we must recognize that there are multiple components to learning, including learning about the specific spatial locations as well as learning about the structure of the cognitive task. Learning about space and learning about task could occur in the same regions, or could occur at very different sites in the circuit. One of our major goals is to explore the neural bases of both spatial and task-related learning. We will use behavioral, electrophysiological and advanced analytical techniques to identify the nature of spatial and task-related neural activity and plasticity across the hippocampal circuit.
The Specific Aims of this proposal are 1) To test the hypothesis that during learning, plasticity in the hippocampal formation changes the place and theta related responses of hippocampal neurons, 2) To test the hypothesis that each region within the hippocampal formation shows a distinct pattern of neural dynamics associated with the formation of new spatial representations, 3) To test the hypothesis that each region within the hippocampal formation shows a distinct pattern of neural dynamics associated with the encoding of task related information. Our overarching hypothesis is that the formation of new representations in the hippocampus is an incremental process, where representations are quickly established in the input and output regions and then elaborated as a result of processing within the circuit. This work will go beyond previous studies to examine the neural dynamics that underlie learning about new places and new tasks. Understanding how the hippocampus participates in learning may help us develop new strategies for treating people with mental impairments related to hippocampal dysfunction, including individuals suffering from schizophrenia as well as children and adults with learning impairments. The study of plasticity in the hippocampal circuit may also help us understand disorders related to abnormal plasticity such as epilepsy.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
3R01MH080283-03S1
Application #
7929322
Study Section
Neurobiology of Learning and Memory Study Section (LAM)
Program Officer
Osborn, Bettina D
Project Start
2009-09-30
Project End
2011-09-29
Budget Start
2009-09-30
Budget End
2011-09-29
Support Year
3
Fiscal Year
2009
Total Cost
$323,402
Indirect Cost
Name
University of California San Francisco
Department
Physiology
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
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Larkin, Margaret Carr; Lykken, Christine; Tye, Lynne D et al. (2014) Hippocampal output area CA1 broadcasts a generalized novelty signal during an object-place recognition task. Hippocampus 24:773-83
Singer, Annabelle C; Carr, Margaret F; Karlsson, Mattias P et al. (2013) Hippocampal SWR activity predicts correct decisions during the initial learning of an alternation task. Neuron 77:1163-73
Kemere, Caleb; Carr, Margaret F; Karlsson, Mattias P et al. (2013) Rapid and continuous modulation of hippocampal network state during exploration of new places. PLoS One 8:e73114
Dabaghian, Y; Memoli, F; Frank, L et al. (2012) A topological paradigm for hippocampal spatial map formation using persistent homology. PLoS Comput Biol 8:e1002581
Carr, Margaret F; Karlsson, Mattias P; Frank, Loren M (2012) Transient slow gamma synchrony underlies hippocampal memory replay. Neuron 75:700-13
Kim, Steve M; Ganguli, Surya; Frank, Loren M (2012) Spatial information outflow from the hippocampal circuit: distributed spatial coding and phase precession in the subiculum. J Neurosci 32:11539-58
Jadhav, Shantanu P; Kemere, Caleb; German, P Walter et al. (2012) Awake hippocampal sharp-wave ripples support spatial memory. Science 336:1454-8
Carr, Margaret F; Jadhav, Shantanu P; Frank, Loren M (2011) Hippocampal replay in the awake state: a potential substrate for memory consolidation and retrieval. Nat Neurosci 14:147-53
Cheng, S; Frank, L M (2011) The structure of networks that produce the transformation from grid cells to place cells. Neuroscience 197:293-306

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