Journal
JOURNAL OF NEUROSCIENCE
Volume 40, Issue 12, Pages 2458-2470Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.2121-19.2020
Keywords
AMPAR; macaque monkey; NMDAR; PFC; working memory
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Funding
- NWO (ALW Grant) [823-02-010]
- European Union (Marie-Curie Action) [PITN-GA-2011290011]
- European Union (Human Brain Project) [7202070, 785907]
- European Union (ERC) [339490]
- Friends Foundation of The Netherlands Institute for Neuroscience
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Many tasks demand that information is kept online for a few seconds before it is used to guide behavior. The information is kept in working memory as the persistent firing of neurons encoding the memorized information. The neural mechanisms responsible for persistent activity are not yet well understood. Theories attribute an important role to ionotropic glutamate receptors, and it has been suggested that NMDARs are particularly important for persistent firing because they exhibit long time constants. lonotropic AMPARs have shorter time constants and have been suggested to play a smaller role in working memory. Here we compared the contribution of AM PARs and NMDARs to persistent firing in the dlPFC of male macaque monkeys performing a delayed saccade to a memorized spatial location. We used iontophoresis to eject small amounts of glutamate receptor antagonists, aiming to perturb, but not abolish, neuronal activity. We found that both AMPARs and NMDARs contributed to persistent activity. Blockers of the NMDARs decreased persistent firing associated with the memory of the neuron's preferred spatial location but had comparatively little effect on the representation of the antipreferred location. They therefore decreased the information conveyed by persistent firing about the memorized location. In contrast, AMPAR blockers decreased activity elicited by the memory of both the preferred and antipreferred location, with a smaller effect on the information conveyed by persistent activity. Our results provide new insights into the contribution of AMPARs and NMDARs to persistent activity during working memory tasks.
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