Reelin and ApoE Receptors Cooperate to Enhance Hippocampal Synaptic Plasticity and Learning*

By E. Weeber, U. Beffert, Chris Jones, Jill M. Christian, Eckart Förster, J. Sweatt, J. Herz. Journal of Biological Chemistry, 2002

639 citations recorded by the source corpus.

Two apolipoprotein E (apoE) receptors, the very low density lipoprotein (VLDL) receptor and apoE receptor 2 (apoER2), are also receptors for Reelin, a signaling protein that regulates neuronal migration during brain development. In the adult brain, Reelin is expressed by GABA-ergic interneurons, suggesting a potential function as a modulator of neurotransmission. ApoE receptors have been indirectly implicated in memory and neurodegenerative disorders because their ligand, apoE, is genetically associated with Alzheimer disease. We have used knockout mice to investigate the role of Reelin and its receptors in cognition and synaptic plasticity. Mice lacking either the VLDL receptor or the apoER2 show contextual fear conditioning deficits. VLDL receptor-deficient mice also have a moderate defect in long term potentiation (LTP), and apoER2 knockouts have a pronounced one. The perfusion of mouse hippocampal slices with Reelin has no effect on baseline synaptic transmission but significantly enhances LTP in area CA1. This Reelin-dependent augmentation of LTP is abolished in VLDL receptor and apoER2 knockout mice. Our results reveal a role for Reelin in controlling synaptic plasticity in the adult brain and suggest that both of its receptors are necessary for Reelin-dependent enhancement of synaptic transmission in the hippocampus. Thus, the impairment of apoE receptor-dependent neuromodulation may contribute to cognitive impairment and synaptic loss in Alzheimer disease.

Subfields: Developmental Neuroscience, Neurology, Physiology

View Paper: https://www.semanticscholar.org/paper/529312ec73bafde5b1861c4abd4376a55b828253

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Developmental Neuroscience

1. J. Sweatt
2. Courtney A. Miller
3. Karl J. Friston
4. G. Bu
5. C. Alberini
6. Michael Joseph Meaney
7. Jian‐Kang Zhu
8. M. Lamb

In Neurology

1. Courtney A. Miller
2. ChrisD . Frith
3. J. Sweatt
4. Klaas E. Stephan
5. Karl J. Friston
6. G. Bu
7. D. Holtzman

In Physiology

1. J. Herz
2. D. Holtzman
3. G. Bu
4. ChrisD . Frith
5. Karl J. Friston
6. Berislav Zlokovic
7. J. Long
8. Martin Citron

Citations in the corpus

• Regulation of extrasynaptic signaling by polysialylated NCAM: Impact for synaptic plasticity and cognitive functions (2017, background): “In particular, Reelin potently enhances CA1 LTP, and this effect is dependent on expression of both, very-low-density lipoprotein receptor (VLDLR) and apolipo-protein E receptor type 2 (ApoER2) (Weeber et al., 2002).”
• Covalent modification of DNA regulates memory formation. (2007, positive): “Fragile X mental retardation results from abnormal trinucleotide expansion, which leads to decreased gene expression through aberrant DNA methylation and restrictive chromatin structure (reviewed in Weeber et al., 2002b).”
• Dysconnection in Schizophrenia: From Abnormal Synaptic Plasticity to Failures of Self-monitoring (2009, background): “More recently, it has become clear that reelin also has important functions in the adult brain where it takes part in the regulation of synaptic plasticity.(215) In particular, reelin is a potent enhancer of NMDAR-dependent synaptic plasticity.”
• Apolipoprotein E and apolipoprotein E receptors: normal biology and roles in Alzheimer disease. (2012, positive): “In addition to effects on the apoE/Ab pathway, apoE receptors such as Apoer2 and Vldlr play important roles in synaptic plasticity, tau phosphorylation, and neuroprotection.”