A prominent hypothesis in cognitive neuroscience is that memories are organized and made permanent in the cerebral cortex via temporary involvement of the hippocampus, a phenomenon called systems consolidation. Although key roles for the cortex and hippocampus are well established, very little is known about the nature of the underlying neural memory representations and how they change during consolidation. Yet, to address disorders of thought and organization of knowledge, it will be crucial to understand how memories are encoded, organized, and consolidated in the normal brain. The proposed experiments are designed to pioneer a new approach to this area by examining current theories of systems memory consolidation by combining state-of-the-art multichannel neuron recording in animals as they learn and remember a series of what- happened-where associations, as well as state-of-the-art techniques for reversible neural inactivation to examine functional interactions between the hippocampus and cortex.
Specific Aim 1 will characterize the nature and organization of neural ensemble memory representations in the cortex and hippocampus and the development of cortical representations in the absence of hippocampal function.
Specific Aim 2 will examine the time-limited role of the hippocampus in the organization and stabilization of cortical memory representations following learning.
Specific Aim 3 will examine the role of consolidation at the cellular and synaptic level on the persistence of neural memory representations in the hippocampus and cortex. These studies will provide the first examination of systems consolidation at the level of neural representations, challenging current views and leading to new insights about this important phenomenon in cognitive function.

Public Health Relevance

Our understanding of cognitive disorders and the eventual development of treatments depends crucially upon an understanding of the cognitive and neural mechanisms that underlie normal cognition;for example, abnormal thought patterns in schizophrenia, as well as other cognitive disorders, reflects an underlying disorganization of the neural machinery that stores and consolidates memories in the schemas that compose our knowledge of the world. The proposed work will pioneer a new understanding about how memories are represented in neural circuitry and about how neural representations are organized into schemas that guide cognition in daily life. Because the hippocampus and adjacent cortical areas are compromised in multiple major mental disorders, an understanding the functional circuitry of these areas is particularly important.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH052090-17
Application #
8249369
Study Section
Neurobiology of Learning and Memory Study Section (LAM)
Program Officer
Osborn, Bettina D
Project Start
1994-09-01
Project End
2016-01-31
Budget Start
2012-02-01
Budget End
2013-01-31
Support Year
17
Fiscal Year
2012
Total Cost
$409,042
Indirect Cost
$159,042
Name
Boston University
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
049435266
City
Boston
State
MA
Country
United States
Zip Code
02215
Howard, Marc W; Eichenbaum, Howard (2015) Time and space in the hippocampus. Brain Res 1621:345-54
McKenzie, Sam; Frank, Andrea J; Kinsky, Nathaniel R et al. (2014) Hippocampal representation of related and opposing memories develop within distinct, hierarchically organized neural schemas. Neuron 83:202-15
Eichenbaum, Howard; Cohen, Neal J (2014) Can we reconcile the declarative memory and spatial navigation views on hippocampal function? Neuron 83:764-70
Preston, Alison R; Eichenbaum, Howard (2013) Interplay of hippocampus and prefrontal cortex in memory. Curr Biol 23:R764-73
McKenzie, Sam; Robinson, Nick T M; Herrera, Lauren et al. (2013) Learning causes reorganization of neuronal firing patterns to represent related experiences within a hippocampal schema. J Neurosci 33:10243-56
McKenzie, Sam; Eichenbaum, Howard (2012) New approach illuminates how memory systems switch. Trends Cogn Sci 16:102-3
Farovik, Anja; Place, Ryan James; Miller, Danielle Renee et al. (2011) Amygdala lesions selectively impair familiarity in recognition memory. Nat Neurosci 14:1416-7
McKenzie, Sam; Eichenbaum, Howard (2011) Consolidation and reconsolidation: two lives of memories? Neuron 71:224-33
Sauvage, Magdalena M; Beer, Zachery; Ekovich, Muriel et al. (2010) The caudal medial entorhinal cortex: a selective role in recollection-based recognition memory. J Neurosci 30:15695-9
Eichenbaum, H; Fortin, N; Sauvage, M et al. (2010) An animal model of amnesia that uses Receiver Operating Characteristics (ROC) analysis to distinguish recollection from familiarity deficits in recognition memory. Neuropsychologia 48:2281-9

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