Impairment of long-term potentiation and spatial memory in leptin receptor-deficient rodents
Abstract
Leptin is well known to be involved in the control of feeding, reproduction and neuroendocrine functions through its action on the hypothalamus. However, leptin receptors are found in brain regions other than the hypothalamus (including the hippocampus and cerebral cortex) suggesting extrahypothalamic functions. We investigated hippocampal long-term potentiation (LTP) and long-term depression (LTD), and the spatial-memory function in two leptin receptor-deficient rodents (Zucker rats and db/db mice). In brain slices, the CA1 hippocampal region of both strains showed impairments of LTP and LTD; leptin (10(-12) M) did not improve these impairments in either strain. These strains also showed lower basal levels of Ca(2+)/calmodulin-dependent protein kinase II activity in the CA1 region than the respective controls, and the levels did not respond to tetanic stimulation. These strains also showed impaired spatial memory in the Morris water-maze test (i.e. longer swim-path lengths during training sessions and less frequent crossings of the platform's original location in the probe test. From these results we suggest that the leptin receptor-deficient animals show impaired LTP in CA1 and poor spatial memory due, at least in part, to a deficiency in leptin receptors in the hippocampus.
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Neural activity in brain areas involved in cognitive processing of food representations, such as the amygdala and hippocampal complex, is modulated by leptin and ghrelin.
“Furthermore, neural activity in brain areas thought to be involved in cognitive processing of representations of food such as the amygdala and hippocampal complex is modulated by leptin ([78](#B78), [79](#B79), [105](#B105)) and ghrelin ([27](#B27), [50](#B50), [92](#B92), [109](#B109), [147](#B147), [189](#B189)).”
From Food reward, hyperphagia, and obesity (2011) · cites this paper as [105]
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- Authors
- Li, X.-L., Aou, S., Oomura, Y., Hori, N., Fukunaga, K., & Hori, T.
- Affiliations
- Kyushu University (JP)
- New York State Department of Health (US)
- Kumamoto University (JP)
- Corresponding author
- Aou, S
- ORCID
- Venue
- Neuroscience
- Publisher
- Elsevier BV
- Published
- 2002-09
- Volume
- 113
- Issue
- 3
- Pages
- 607-615
- ISSN
- 0306-4522 (ISSN-L)
- OpenAlex
- W1987248538
- Semantic Scholar
- 75386d6a267ff04ec52feace903c30100136eeba
- Cited by
- 440
- References
- 71
- Citations by year
- 2026: 2 · 2025: 14 · 2024: 14 · 2023: 10 · 2022: 12 · 2021: 21 · 2020: 14 · 2019: 27 · 2018: 29 · 2017: 29 · 2016: 21 · 2015: 35 · 2014: 29 · 2013: 30 · 2012: 21
- FWCI
- 2.79
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- leptin, leptin receptor deficiency, long-term potentiation, long-term depression, spatial memory, hippocampus, CA1, CaMKII, db/db mice, Zucker rats, tetanic stimulation
- MeSH terms
- Animals, Electrophysiology, Hippocampus, Memory, Mice, Inbred C57BL, Receptors, Cell Surface, Spatial Behavior, Water, Long-Term Potentiation, Mice, Knockout, Maze Learning, Long-Term Synaptic Depression, Mice, Rats, Receptors, Leptin
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