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Impaired discrimination learning in interneuronal NMDAR-GluN2B mutant mice
Jonathan L Brigman1, Rachel A Daut, Lisa Saksida
1aDepartment of Neurosciences, University of New Mexico School of Medicine, Albuquerque, New Mexico bLaboratory of Behavioral and Genomic Neuroscience, NIAAA, NIH Rockville, Maryland cDepartment of Psychiatry, University of Alabama School of Medicine, Birmingham, Alabama, USA dDepartment of Experimental Psychology, Medical Research Council and Wellcome Trust Behavioral and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK.
Loss of GluN2B-containing N-methyl-D-aspartate receptors (NMDARs) on GABAergic interneurons impairs associative learning. This highlights the critical role of these specific NMDARs in modulating striatal function for efficient choice behavior.
Area of Science:
- Neuroscience
- Molecular Biology
- Behavioral Science
Background:
- N-methyl-D-aspartate receptors (NMDARs) containing the GluN2B subunit are crucial for learning.
- NMDARs on GABAergic interneurons may regulate striatal function, balancing action and excitation.
- Understanding this specific NMDAR subtype's role in interneurons is key to deciphering learning mechanisms.
Purpose of the Study:
- To investigate the impact of GluN2B-containing NMDAR loss on GABAergic interneurons in corticostriatal associative learning.
- To determine how altered NMDAR function in interneurons affects learning behaviors.
Main Methods:
- Generated mutant mice with targeted deletion of GluN2B on forebrain interneurons (floxed-GluN2B×Ppp1r2-Cre).
- Utilized a touchscreen-based pairwise visual learning paradigm for behavioral phenotyping.
- Analyzed performance during Pavlovian, instrumental pretraining, and discrimination learning tasks.
Main Results:
- Mutant mice exhibited normal performance in initial learning phases (Pavlovian and instrumental pretraining).
- Significant impairment was observed in the discrimination learning task for the mutants.
- Reduced win-stay behavior was a key characteristic of the mutants' impaired discrimination performance.
Conclusions:
- The study confirms the importance of NMDARs, particularly GluN2B, in modulating striatal function for effective choice behavior.
- NMDARs located on interneurons play a critical role in the complex processes of associative learning.
- Targeting NMDARs on interneurons presents a potential avenue for understanding and treating learning deficits.
