Dataset Information

Postsynaptic ?1 glutamate receptor assembles and maintains hippocampal synapses via Cbln2 and neurexin.

ABSTRACT: The ?1 glutamate receptor (GluD1) was cloned decades ago and is widely expressed in many regions of the brain. However, its functional roles in these brain circuits remain unclear. Here, we find that GluD1 is required for both excitatory synapse formation and maintenance in the hippocampus. The action of GluD1 is absent in the Cbln2 knockout mouse. Furthermore, the GluD1 actions require the presence of presynaptic neurexin 1? carrying the splice site 4 insert (+S4). Together, our findings demonstrate that hippocampal synapse assembly and maintenance require a tripartite molecular complex in which the ligand Cbln2 binds with presynaptic neurexin 1? (+S4) and postsynaptic GluD1. We provide evidence that this mechanism may apply to other forebrain synapses, where GluD1 is widely expressed.

SUBMITTER: Tao W

PROVIDER: S-EPMC6003362 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Postsynaptic δ1 glutamate receptor assembles and maintains hippocampal synapses via Cbln2 and neurexin.

Tao Wucheng W Díaz-Alonso Javier J Sheng Nengyin N Nicoll Roger A RA

Proceedings of the National Academy of Sciences of the United States of America 20180521 23

The δ1 glutamate receptor (GluD1) was cloned decades ago and is widely expressed in many regions of the brain. However, its functional roles in these brain circuits remain unclear. Here, we find that GluD1 is required for both excitatory synapse formation and maintenance in the hippocampus. The action of GluD1 is absent in the Cbln2 knockout mouse. Furthermore, the GluD1 actions require the presence of presynaptic neurexin 1β carrying the splice site 4 insert (+S4). Together, our findings demons ...[more]

PMID: 29784783

Similar Datasets

Project description:Mounting evidence suggests that synaptic plasticity provides the cellular biological basis of learning and memory, and plasticity deficits play a key role in dementia caused by Alzheimer's disease. However, the mechanisms by which synaptic dysfunction contributes to the pathogenesis of Alzheimer's disease remain unclear. In the present study, Alzheimer's disease transgenic mice were used to determine the relationship between decreased hippocampal synaptic plasticity and pathological changes and cognitive-behavioral deterioration, as well as possible mechanisms underlying decreased synaptic plasticity in the early stages of Alzheimer's disease-like diseases. APP/PS1 double transgenic (5XFAD; Jackson Laboratory) mice and their littermates (wild-type, controls) were used in this study. Additional 6-week-old and 10-week-old 5XFAD mice and wild-type mice were used for electrophysiological recording of hippocampal dentate gyrus. For 10-week-old 5XFAD mice and wild-type mice, the left hippocampus was used for electrophysiological recording, and the right hippocampus was used for biochemical experiments or immunohistochemical staining to observe synaptophysin levels and amyloid beta deposition levels. The results revealed that, compared with wild-type mice, 6-week-old 5XFAD mice exhibited unaltered long-term potentiation in the hippocampal dentate gyrus. Another set of 5XFAD mice began to show attenuation at the age of 10 weeks, and a large quantity of amyloid beta protein was accumulated in hippocampal cells. The location of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor and N-methyl-D-aspartic acid receptor subunits in synaptosomes was decreased. These findings indicate that the delocalization of postsynaptic glutamate receptors and an associated decline in synaptic plasticity may be key mechanisms in the early onset of Alzheimer's disease. The use and care of animals were in strict accordance with the ethical standards of the Animal Ethics Committee of Capital Medical University, China on December 17, 2015 (approval No. AEEI-2015-182).

Dataset Information

Postsynaptic ?1 glutamate receptor assembles and maintains hippocampal synapses via Cbln2 and neurexin.

Publications

Postsynaptic δ1 glutamate receptor assembles and maintains hippocampal synapses via Cbln2 and neurexin.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets