Related Experiment Video
Updated: Jun 12, 2025
07:03
Evaluation of Hemisphere Lateralization with Bilateral Local Field Potential Recording in Secondary Motor Cortex of Mice
Published on: July 31, 2019
6.7K
Grin2a Hypofunction Impairs Spatial Working Memory and Disrupts Hippocampal Network Oscillations and
Hassan Hosseini1, Sky Evans-Martin1, Emma Bogomilsky1
1Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan.
Biological Psychiatry Global Open Science
|June 10, 2025
Summary
Disrupting the GRIN2A gene impairs working memory and hippocampal network function. This involves altered brain oscillations and excitatory/inhibitory balance, potentially linking to cognitive disorders.
Area of Science:
- Neuroscience
- Molecular Biology
- Cognitive Science
Background:
- NMDA receptors with the GluN2A subunit are crucial for learning, memory, and cognitive functions like working memory.
- The GRIN2A gene encodes the GluN2A subunit, essential for maintaining these cognitive abilities.
Purpose of the Study:
- To investigate how deleting the mouse Grin2a gene affects working memory.
- To examine the impact of Grin2a gene ablation on hippocampal network oscillations and excitatory/inhibitory (E/I) balance.
Main Methods:
- Spatial working memory was assessed in Grin2a mutant mice using the 8-arm radial maze.
- Multielectrode arrays and whole-cell patch-clamp electrophysiology were used to analyze hippocampal slices.
- Immunohistochemistry identified changes in GABAergic neuron populations.
Main Results:
- Grin2a deficiency led to impaired spatial working memory and disrupted theta-gamma oscillation coupling in the hippocampus.
- Mutant mice showed an overabundance of parvalbumin-expressing interneurons.
- This imbalance destabilized the E/I input to CA1 pyramidal neurons.
Conclusions:
- GluN2A-containing NMDA receptors are vital for hippocampal network synchrony.
- Disrupted network synchrony and E/I balance in the hippocampus may underlie cognitive deficits in Grin2a-related disorders.
- These findings link Grin2a gene function to conditions like schizophrenia, epilepsy, and intellectual disability.
