RGD Reference Report - Differential reelin-induced enhancement of NMDA and AMPA receptor activity in the adult hippocampus. - Rat Genome Database

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Differential reelin-induced enhancement of NMDA and AMPA receptor activity in the adult hippocampus.

Authors: Qiu, S  Zhao, LF  Korwek, KM  Weeber, EJ 
Citation: Qiu S, etal., J Neurosci. 2006 Dec 13;26(50):12943-55.
RGD ID: 4108507
Pubmed: (View Article at PubMed) PMID:17167084
DOI: Full-text: DOI:10.1523/JNEUROSCI.2561-06.2006

The developmental lamination of the hippocampus and other cortical structures requires a signaling cascade initiated by reelin and its receptors, apoER2 (apolipoprotein E receptor 2) and VLDLR (very-low-density lipoprotein receptor). However, the functional significance of continued reelin expression in the postnatal brain remains poorly understood. Here, we show that reelin application to adult mice hippocampal slices leads to enhanced glutamatergic transmission mediated by NMDA receptors (NMDARs) and AMPA receptors (AMPARs) through distinct mechanisms. Application of recombinant reelin enhanced NMDAR-mediated currents through postsynaptic mechanisms, as revealed by the variance-mean analysis of synaptic NMDAR currents, assessment of spontaneous miniature events, and the levels of NMDAR subunits at synaptic surface. In comparison, nonstationary fluctuation analysis of miniature AMPAR currents and quantification of synaptic surface proteins revealed that reelin-induced enhancement of AMPAR responses was mediated by increased AMPAR numbers. Reelin enhancement of synaptic NMDAR currents was abolished when receptor-associated protein (RAP) or the Src inhibitor 4-amino-5-(4-methylphenyl)-7-(t-butyl)pyrazolo[3,4-d]-pyrimidine (PP1) was bath applied and was abrogated by including PP1 in the recording electrodes. In comparison, including RAP or an inactive PP1 analog PP3 in the recording electrode was without effect. Interestingly, the increased AMPAR response after reelin application was not blocked by PP1 but was blocked by the phosphoinositide-3' kinase (PI3K) inhibitors wortmannin and LY294002 [2-(4-morpholinyl)-8-phenyl-1(4H)-benzopyran-4-one hydrochloride]. Furthermore, reelin-induced, PI3K-dependent AMPAR surface insertion was also observed in cultured hippocampal neurons. Together, these results reveal a differential functional coupling of reelin signaling with NMDAR and AMPAR function and define a novel mechanism for controlling synaptic strength and plasticity in the adult hippocampus.

Molecular Pathway Annotations    
Objects Annotated

Genes (Rattus norvegicus)
Pik3r1  (phosphoinositide-3-kinase regulatory subunit 1)

Genes (Mus musculus)
Pik3r1  (phosphoinositide-3-kinase regulatory subunit 1)

Genes (Homo sapiens)
PIK3R1  (phosphoinositide-3-kinase regulatory subunit 1)

Additional Information