The Contribution of AMPA and NMDA Receptors to Persistent Firing in the Dorsolateral Prefrontal Cortex in Working Memory

Abstract

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. Ionotropic AMPARs have shorter time constants and have been suggested to play a smaller role in working memory. Here we compared the contribution of AMPARs 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.

Regional brain gray matter volume in world-class artistic gymnasts

“…Our findings support the concept that long-term motor skill training is associated with a complex bihemispheric cortical-subcortical network [2,18]. The brain areas identified in this study are functionally related to motor control (i.e., PrG) [19,20], interpretation of sensory information (i.e., IPL) [21][22][23], body image (i.e., IPL) [21,22], spatial perception (i.e., IPL and MTG) [23,24], spatial attention (i.e., IPL) [21][22][23], vision (i.e., IPL and MTG) [21][22][23][24], executive function (i.e., RMFG and IPL) [22,[25][26][27], and working memory (i.e., RMFG and SFG) [25][26][27][28]. A unique feature of gymnastics events is that each requires acrobatic performances comprising speed, strength, and flexibility; these physiological functions are all critical to supporting elaborate body movements.…”

“…The IPL is known to be involved in various neural functions, including spatial attention, multimodal sensory integration, body image, oculomotor control, and hand-eye coordination [21][22][23]. The RMFG is critical for executive function and working memory [25][26][27]. Working memory is a series of memory operations that involve manipulating and utilizing information while temporarily retaining it in the brain.…”

Neuronal timescales are functionally dynamic and shaped by cortical microarchitecture

“…Theoretical accounts posit that NMDA-mediated recurrent excitation coupled with fast inhibition (Chaudhuri et al, 2015;Wang, 1999Wang, , 2008, as well as cell-intrinsic properties (Duarte and Morrison, 2019;Gjorgjieva et al, 2016;Koch et al, 1996), are crucial for shaping neuronal timescales. While in vitro and in vivo studies in model organisms (van Vugt et al, 2020;Wang et al, 2013) can test these hypotheses at the single-neuron level, causal manipulation and large-scale recording of neuronal networks embedded in the human brain is severely limited. Here, we apply an approach analogous to multimodal single-cell profiling (Bomkamp et al, 2019) and examine the transcriptomic basis of neuronal dynamics at the macroscale.…”

Using rat operant delayed match-to-sample task to identify neural substrates recruited with increased working memory load

“…In this regard, a recent study by (Woodcock et al 2018) showed that glutamate levels rise in the human dlPFC in response to increased WM demand. On the other hand, inhibiting glutamate release via local administration of mGlu2/3 (auto)receptor agonists, or blockade of the postsynaptic ionotropic glutamate receptors disrupted sustained firing of local pyramidal neurons and impaired WM performance in animals (Gregory et al 2003;van Vugt et al 2020;Wang et al 2013). Recent studies by our laboratory and others, showed that systemic or local intra-PrL inhibition of mGlu5 receptors impairs DMS task performance Hámor et al 2020;Hernandez et al 2018).…”