Synaptic plasticity and cognitive function are disrupted in the absence of Lrp4
Open accessAbstract
Lrp4, the muscle receptor for neuronal Agrin, is expressed in the hippocampus and areas involved in cognition. The function of Lrp4 in the brain, however, is unknown, as Lrp4−/− mice fail to form neuromuscular synapses and die at birth. Lrp4−/− mice, rescued for Lrp4 expression selectively in muscle, survive into adulthood and showed profound deficits in cognitive tasks that assess learning and memory. To learn whether synapses form and function aberrantly, we used electrophysiological and anatomical methods to study hippocampal CA3–CA1 synapses. In the absence of Lrp4, the organization of the hippocampus appeared normal, but the frequency of spontaneous release events and spine density on primary apical dendrites were reduced. CA3 input was unable to adequately depolarize CA1 neurons to induce long-term potentiation. Our studies demonstrate a role for Lrp4 in hippocampal function and suggest that patients with mutations in Lrp4 or auto-antibodies to Lrp4 should be evaluated for neurological deficits.
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Mice expressing Lrp4 in muscle on an Lrp4 knockout background show reduced synaptic transmission and long-term potentiation.
“these mice have a reduction of synaptic transmission and long-term potentiation [93]”
From ApoE, ApoE Receptors, and the Synapse in Alzheimer's Disease (2017) · cites this paper as [93]
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- Authors
- Gomez, A. M., Froemke, R. C., & Burden, S. J.
- Affiliations
- NYU Langone Health (US)
- Corresponding author
- Burden, Steven J
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2014-11-19
- Volume
- 3
- Pages
- e04287-e04287
- ISSN
- 2050-084X (ISSN-L)
- PMC
- PMC4270049
- OpenAlex
- W2117504532
- Cited by
- 47
- References
- 49
- Citations by year
- 2026: 1 · 2024: 4 · 2023: 5 · 2022: 9 · 2021: 7 · 2020: 2 · 2019: 2 · 2018: 5 · 2017: 5 · 2016: 4 · 2015: 3
- FWCI
- 1.83
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- eLife (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- eScholarship (California Digital Library) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Funders
- Alfred P. Sloan Foundation (Sloan Foundation) (Robert Froemke)
- National Institute of Neurological Disorders and Stroke (NS36193)
- National Cancer Institute (P30CA16087)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- LRP4, synaptic plasticity, learning and memory, hippocampus, CA3-CA1 synapses, long-term potentiation, dendritic spine density, cognitive impairment
- MeSH terms
- Animals, Animals, Newborn, Cognition, Membranes, Memory, Mice, Mutant Strains, Muscles, Synaptic Transmission, Neuronal Plasticity, Receptors, LDL, Long-Term Potentiation, Maze Learning, LDL-Receptor Related Proteins, Dendritic Spines, CA1 Region, Hippocampal
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