ArticleNeuropharmacology2021
Attenuated NMDAR signaling on fast-spiking interneurons in prefrontal cortex contributes to age-related decline of cognitive flexibility.
Article in Neuropharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 21 citations in OpenAlex.
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- Use of Quantitative Electroencephalography to Inform Age- and Sex-Related Differences in NMDA Receptor Function Following MK-801 Administration.Pharmaceuticals (Basel, Switzerland) · 2024Article
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- Aging or chronic stress impairs working memory and modulates GABA and glutamate gene expression in prelimbic cortex.Frontiers in aging neuroscience · 2023Article
- Age-Related Changes in Risky Decision Making and Associated Neural Circuitry in a Rat Model.eNeuro · 2023Article
- GABANeuropharmacology · 2022Article
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Authors and funding
6 authors at 3 institutions in 1 country.
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Abstract
Ionotropic glutamate receptors of the NMDA and AMPA subtypes transduce excitatory signaling on neurons in the prefrontal cortex (PFC) in support of cognitive flexibility. Cognitive flexibility is reliably observed to decline at advanced ages, coinciding with changes in PFC glutamate receptor expression and neuronal physiology. However, the relationship between age-related impairment of cognitive flexibility and changes to excitatory signaling on distinct classes of PFC neurons is not known. In this study, one cohort of young adult (4 months) and aged (20 months) male F344 rats were characterized for cognitive flexibility on an operant set-shifting task. Expression of the essential NMDAR subunit, NR1, was correlated with individual differences in set-shifting abilities such that lower NR1 in the aged PFC was associated with worse set-shifting. In contrast, lower expression of two AMPAR subunits, GluR1 and GluR2, was not associated with set-shift abilities in aging. As NMDARs are expressed by both pyramidal cells and fast-spiking interneurons (FSI) in PFC, whole-cell patch clamp recordings were performed in a second cohort of age-matched rats to compare age-associated changes on these neuronal subtypes. Evoked excitatory postsynaptic currents were generated using a bipolar stimulator while AMPAR vs. NMDAR-mediated components were isolated using pharmacological tools. The results revealed a clear increase in AMPA/NMDA ratio in FSIs that was not present in pyramidal neurons. Together, these data indicate that loss of NMDARs on interneurons in PFC contributes to age-related impairment of cognitive flexibility.
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