Related Experiment Video

Updated: Mar 14, 2026

Preparation of Oligomeric β-amyloid1-42 and Induction of Synaptic Plasticity Impairment on Hippocampal Slices
04:41

Preparation of Oligomeric β-amyloid1-42 and Induction of Synaptic Plasticity Impairment on Hippocampal Slices

Published on: July 14, 2010

24.1K

Amyloid-β effects on synapses and memory require AMPA receptor subunit GluA3

Niels R Reinders1, Yvonne Pao2, Maria C Renner1

  • 1Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences, Amsterdam, 1105BA, The Netherlands.

Proceedings of the National Academy of Sciences of the United States of America
|October 7, 2016
PubMed

Insights

Amyloid-beta (Aβ) causes cognitive deficits in Alzheimer's disease by impacting AMPA receptor subunit GluA3. Removing GluA3 protects against Aβ-induced synaptic and memory impairments in mouse models.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Pathology

Background:

  • Amyloid-beta (Aβ) oligomers are implicated in early Alzheimer's disease (AD) cognitive decline.
  • Aβ-induced synaptic degradation and memory impairment are observed in AD mouse models.

Purpose of the Study:

  • To investigate the role of AMPA receptor (AMPAR) subunit GluA3 in mediating Aβ-driven synaptic and cognitive deficits.
  • To determine if GluA3 is essential for Aβ toxicity in the brain.

Main Methods:

  • Utilized AD mouse models and hippocampal neuron cultures.
  • Examined synaptic depression, spine loss, and long-term potentiation in the presence and absence of GluA3.
  • Assessed memory function in GluA3-deficient and wild-type mice exposed to Aβ.

Main Results:

  • Aβ-induced synaptic depression and spine loss were prevented in neurons lacking GluA3.
  • Aβ oligomers blocked long-term potentiation exclusively in neurons expressing GluA3.
  • GluA3-deficient mice did not exhibit memory impairment despite Aβ overproduction.

Conclusions:

  • The GluA3 subunit of AMPARs is critical for mediating the detrimental effects of Aβ on synapses.
  • Targeting GluA3-containing AMPARs may offer a therapeutic strategy for Alzheimer's disease.
  • Synaptic and cognitive deficits in early AD are dependent on the presence of GluA3.
Keywords:
AMPAAlzheimeramyloidsynapse

More Related Videos

A High-content Assay for Monitoring AMPA Receptor Trafficking10:34

A High-content Assay for Monitoring AMPA Receptor Trafficking

Published on: January 28, 2019

8.1K
Stereotaxic Infusion of Oligomeric Amyloid-beta into the Mouse Hippocampus08:16

Stereotaxic Infusion of Oligomeric Amyloid-beta into the Mouse Hippocampus

Published on: June 17, 2015

19.4K

Related Concept Videos

Ligand-Gated Ion Channel Receptor: Gating Mechanism01:30

Ligand-Gated Ion Channel Receptor: Gating Mechanism

Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...
4.5K
Amyloid Fibrils03:03

Amyloid Fibrils

Amyloid fibrils are aggregates of misfolded proteins.  Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils. 
Amyloid deposits were observed as early as 1639 in the liver and the spleen.   In 1854, Rudolph Virchow performed iodine staining,...
12.5K
Role of Neurotransmitters in Memory01:23

Role of Neurotransmitters in Memory

Neurotransmitters are integral to the brain's communication system, enabling neurons to transmit signals across synapses. This chemical exchange underpins various cognitive functions, including memory processes. The role of neurotransmitters in memory is multifaceted, influencing the encoding, consolidation, and retrieval of memories through their action on different neural circuits.
 Glutamate and Synaptic Plasticity
Glutamate, the brain's main excitatory neurotransmitter, is...
2.8K
Ligand-gated Ion Channels01:19

Ligand-gated Ion Channels

Ligand-gated ion channels are transmembrane proteins with a channel for ions to pass through and a binding site for a ligand. The channel opens only when a ligand attaches to the binding site.
Three Subfamilies of Ligand-gated Ion Channels
Ligand-gated ion channels fall into three subfamilies. The 'Cys-loop' includes the nicotinic acetylcholine receptors, γ-aminobutyric acid (GABA), glycine, and 5-hydroxytryptamine receptors. The second one is the 'Pore-loop' channels that...
15.1K
Long-term Potentiation01:35

Long-term Potentiation

Long-term potentiation, or LTP, is one of the ways by which synaptic plasticity—changes in the strength of chemical synapses—can occur in the brain. LTP is the process of synaptic strengthening that occurs over time between pre- and postsynaptic neuronal connections. The synaptic strengthening of LTP works in opposition to the synaptic weakening of long-term depression (LTD) and together are the main mechanisms that underlie learning and memory.
59.2K