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.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
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Neurobiology of Learning and Memory Study Section (LAM)
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Osborn, Bettina D
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University of California San Francisco
Schools of Medicine
San Francisco
United States
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Dabaghian, Yuri; Brandt, Vicky L; Frank, Loren M (2014) Reconceiving the hippocampal map as a topological template. Elife 3:e03476
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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
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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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