Studies are proposed to investigate the structure and function of mammalian memory systems. We propose neuropsychological studies of amnesic patients and patients with Parkinson's disease, studies of human eyeblink conditioning, functional magnetic resonance imaging studies, and new studies in the rat, which will complement the studies in humans. The work is organized as five topics.. 1. The organization of declarative memory proposes seven experiments that concern medial temporal lobe function: a) episodic and semantic memory; b) the functions of the perirhinal cortex; c) the problem of task classification; d) the hypothesis that declarative memory is flexible and non-declarative memory, less flexible. 2. Non-declarative memory as an independent entity proposes three experiments concerning a) category (prototype) learning and b) conceptual priming. 3. Eyeblink conditioning proposes four experiments to pursue our finding that awareness of the stimulus contingencies is a prerequisite for differential trace conditioning. We propose to study a) single-cue conditioning; b) the development of awareness during conditioning; c) trace conditioning in amnesia; d) the effects of divided attention on retention of trace conditioning. 4. Declarative and non- declarative memory as revealed in fMRI proposes five experiments using blocked and event-related techniques. We will a) compare perceptual priming and recognition; b) compare priming and recognition in amnesia; and c) study medial temporal lobe activation during retrieval as a function of retention interval. 5. Complementary studies in rats proposes six experiments in our newly operational rat laboratory (up and going since March, 1998. We will assess visual recognition memory following ibotenic or radio-frequency lesions of the hippocampus using a) non- matching to sample; b) the visual paired-comparison task; c) the socially- acquired food preference task . We will also d) determine the locus and size of the effective lesion in the case of task (b) and compare the findings to what has been determined for a spatial task (Moser et al. 1993). Finally 3), we will study the temporal gradient of retrograde amnesia. It is worth noting that a key component of the work in humans is the availability of two profoundly amnesic patients who have no capacity for declarative memory. A second key component of our program is our new work with rats, which is conceptually closely related to our work with humans.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-IFCN-7 (01))
Program Officer
Kurtzman, Howard S
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of California San Diego
Schools of Medicine
La Jolla
United States
Zip Code
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

Showing the most recent 10 out of 204 publications