Related Experiment Video
Updated: May 11, 2026

Single Synapse Indicators of Glutamate Release and Uptake in Acute Brain Slices from Normal and Huntington Mice
Published on: March 11, 2020
Protein kinase Mζ-dependent maintenance of GluA2 at the synapse: a possible target for preventing or treating
1Department for Life Quality Studies, University of Bologna, 40127 Bologna, Italy. giorgio.aicardi@unibo.it
Abstract:
Age-related functional alterations in the perforant path projection from the entorhinal cortex to the dentate gyrus (DG) of the hippocampus play a major role in age-related memory impairments, but little is known about the molecular mechanisms responsible for these changes. In a recent interesting study, Hara and colleagues (J Neurosci 2012;32:7336-7344) tested young and aged monkeys on the visual recognition memory test "delayed nonmatching-to-sample" (DNMS). Then they performed electron microscopy immunocytochemistry in the hippocampal DG to determine the subcellular localization of the GluA2 subunit of the glutamate α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor (AMPAR) and protein kinase Mζ (PKMζ), which promotes memory storage by regulating GluA2-containing AMPAR trafficking. The results obtained suggest that age-related deficits in visual recognition memory are coupled with impairment in PKMζ-dependent maintenance of GluA2 at the synapse. Together with previous evidence of the critical role of PKMζ in memory consolidation, these data render this enzyme an attractive potential therapeutic target for preventing or treating age-related memory decline, and support the view that the pharmacological manipulation of AMPAR trafficking in the synapses may provide new insights in the search of memory enhancers for aged individuals, including those affected by Alzheimer disease.
Insights
Age-related memory decline is linked to synaptic issues in the hippocampus. Impaired protein kinase Mζ (PKMζ) function disrupts glutamate receptor GluA2 maintenance, affecting memory storage and recognition.
Area of Science:
- Neuroscience
- Molecular Biology
- Gerontology
Background:
- Age-related memory impairments are significant, yet molecular mechanisms remain unclear.
- The perforant path projection in the hippocampus is crucial for memory and shows age-related functional changes.
- Understanding these changes is vital for developing interventions for cognitive decline.
Purpose of the Study:
- To investigate the molecular mechanisms underlying age-related memory deficits.
- To examine the role of protein kinase Mζ (PKMζ) and GluA2 subunit of AMPA receptors in age-related memory decline.
- To assess synaptic changes in the hippocampus of young and aged monkeys.
Main Methods:
- Delayed nonmatching-to-sample (DNMS) test to assess visual recognition memory in young and aged monkeys.
- Electron microscopy immunocytochemistry in the hippocampal dentate gyrus (DG).
- Determination of the subcellular localization of GluA2 and PKMζ.
Main Results:
- Aged monkeys exhibited deficits in visual recognition memory compared to young monkeys.
- Age-related memory decline was associated with impaired PKMζ-dependent maintenance of GluA2 at the synapse.
- Reduced GluA2 localization at synapses in aged individuals suggests impaired AMPA receptor trafficking.
Conclusions:
- Age-related memory deficits are linked to synaptic dysfunction involving PKMζ and AMPA receptor trafficking.
- PKMζ is a potential therapeutic target for preventing or treating age-related memory decline.
- Pharmacological manipulation of AMPA receptor trafficking may offer strategies for memory enhancement in aging and Alzheimer's disease.
More Related Videos
14:57Preparation of Acute Hippocampal Slices from Rats and Transgenic Mice for the Study of Synaptic Alterations during Aging and Amyloid Pathology
Published on: March 23, 2011
08:30Preparation of Synaptoneurosomes from Mouse Cortex using a Discontinuous Percoll-Sucrose Density Gradient
Published on: September 17, 2011
Related Concept Videos
Long-term Depression
Calcium Ion Concentration Mechanism
If over time, all...
Long-term Depression