Studies are proposed to improve understanding of the structure, organization, and function of mammalian memory systems and the nature of memory disorders. The work is organized as 6 separate topics: 1) the organization of declarative memory;the hippocampus;2) the organization of declarative memory;the medial temporal lobe;3) memory, awareness, and measures of eye movements;4) conjoint fMRI studies and lesion studies;5) classical eyeblink conditioning;6) studies with rodents, which will complement the studies in humans. Salient among the proposed plans is a novel direction of research for this laboratory to determine to what extent and how eye movements (e.g., as one scans a recently encountered scene) might reveal experience-dependent effects. What kind of declarative or non-declarative memory is indexed by eye movements? Also salient among the proposed plans is a program of study of the rat hippocampus, perirhinal cortex, and postrhinal cortex (and also the caudate nucleus), which is intended to address a number of longstanding issues that arise from the tradition of human neuropsychological studies. Studies are proposed of discrimination learning, remote spatial memory, and visual recognition memory, which are intended to address a number of long-standing issues. Another salient part of the proposed plans are studies intended to improve the interpretational power of fMRI, which on its own provides correlation data. Specifically, fMRI studies of hippocampus and medial temporal lobe are proposed in which the identical experimental design used in fMRI will also be used (outside the scanner) with amnesic study patients who have damage limited to the hippocampal region. A key component of the work is the availability of amnesic study patients, whose lesions have been described in considerable anatomical and quantitative detail. Up to 7 patients are available whose damage is limited to the hippocampal region, and 2 others (E.P. and G.P.) are of interest because they have large medial temporal lobe lesions and virtually no capacity for declarative memory. A second key component of the work is the close conceptual relationship between the rodent program and the work with humans.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH024600-36
Application #
7616074
Study Section
Neurobiology of Learning and Memory Study Section (LAM)
Program Officer
Osborn, Bettina D
Project Start
1979-01-01
Project End
2010-12-31
Budget Start
2009-05-01
Budget End
2010-12-31
Support Year
36
Fiscal Year
2009
Total Cost
$724,273
Indirect Cost
Name
University of California San Diego
Department
Psychiatry
Type
Schools of Medicine
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Urgolites, Zhisen J; Hopkins, Ramona O; Squire, Larry R (2017) Medial temporal lobe and topographical memory. Proc Natl Acad Sci U S A 114:8626-8630
Squire, Larry R (2017) Memory for relations in the short term and the long term after medial temporal lobe damage. Hippocampus 27:608-612
Ocampo, Amber C; Squire, Larry R; Clark, Robert E (2017) Hippocampal area CA1 and remote memory in rats. Learn Mem 24:563-568
Smith, Christine N; Squire, Larry R (2017) When eye movements express memory for old and new scenes in the absence of awareness and independent of hippocampus. Learn Mem 24:95-103
Urgolites, Zhisen J; Kim, Soyun; Hopkins, Ramona O et al. (2016) Map reading, navigating from maps, and the medial temporal lobe. Proc Natl Acad Sci U S A 113:14289-14293
Sapiurka, Maya; Squire, Larry R; Clark, Robert E (2016) Distinct roles of hippocampus and medial prefrontal cortex in spatial and nonspatial memory. Hippocampus 26:1515-1524
Dede, Adam J O; Wixted, John T; Hopkins, Ramona O et al. (2016) Autobiographical memory, future imagining, and the medial temporal lobe. Proc Natl Acad Sci U S A 113:13474-13479
Dede, Adam J O; Frascino, Jennifer C; Wixted, John T et al. (2016) Learning and remembering real-world events after medial temporal lobe damage. Proc Natl Acad Sci U S A 113:13480-13485
Smith, Christine N; Jeneson, Annette; Frascino, Jennifer C et al. (2014) When recognition memory is independent of hippocampal function. Proc Natl Acad Sci U S A 111:9935-40
Smith, Christine N (2014) Retrograde memory for public events in mild cognitive impairment and its relationship to anterograde memory and neuroanatomy. Neuropsychology 28:959-72

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