A dopamine gradient controls access to distributed working memory in monkey cortex

Abstract

SummaryDopamine is critical for working memory. However, its effects throughout the large-scale primate cortex are poorly understood. Here we report that dopamine receptor density per neuron, measured by receptor autoradiography in the macaque monkey cortex, displays a macroscopic gradient along the cortical hierarchy. We developed a connectome- and biophysically-based model for distributed working memory that incorporates multiple neuron types and a dopamine gradient. The model captures an inverted U-shaped dependence of working memory on dopamine. The spatial distribution of mnemonic persistent activity matches that observed in over 90 experimental studies. We show that dopamine filters out irrelevant stimuli by enhancing inhibition of pyramidal cell dendrites. The level of cortical dopamine can also determine whether memory encoding is through persistent activity or an internal synaptic state. Taken together, our work represents a cross-level understanding that links molecules, cell types, recurrent circuit dynamics and a core cognitive function distributed across the cortex.

Gradients of receptor expression in the macaque cortex

“…Despite these advances, our theoretical understanding of how distinct cognitive functions emerge across different areas of the cortex is limited. The large-scale receptor data presented here can provide an anatomical basis for future large-scale models of neuromodulation of brain connectivity (Deco et al, 2018), activity and cognitive function (Cano-Colino et al, 2014;Froudist-Walsh et al, 2020) and for understanding the emergence of flexible higher cognition along the cortical hierarchy.…”

“…Gradients of connectivity (Margulies et al, 2016;Xu et al, 2020), cell-type densities (Kim et al, 2017), receptor expression (Goulas et al, 2021) and gene expression (Burt et al, 2018;Fulcher et al, 2019) have been described. Many of these properties vary along an axis that aligns with the cortical hierarchy, which can be estimated based on patterns of laminar connectivity (Felleman and Van Essen, 1991;Froudist-Walsh et al, 2020;Markov et al, 2014b;Theodoni et al, 2020). One of the mysteries of such organization is how gradual changes in anatomical properties can lead to the emergence of strikingly different functions.…”

“…This database is regularly updated with new connectivity data (Markov et al, 2014a). We recently estimated the cortical hierarchy using this data, based on the laminar patterns of connections (Froudist-Walsh et al, 2020). For details of the method, please see (Froudist-Walsh et al, 2020;Markov et al, 2014b).…”

“…We recently estimated the cortical hierarchy using this data, based on the laminar patterns of connections (Froudist-Walsh et al, 2020). For details of the method, please see (Froudist-Walsh et al, 2020;Markov et al, 2014b). The parcellation for this connectivity data (the Lyon Macaque Brain Atlas; known in BALSA as the M132 atlas) has previously been made available on the Yerkes19 surface (Donahue et al, 2016).…”

Combining Brain Perturbation and Neuroimaging in Non-human Primates

“…The combination of these techniques with invasive and post-mortem anatomy has also begun to reveal cellular mechanisms underlying post-lesion recovery dynamics. These studies can be used to inform and test computational models of lesion effects and post-lesion plasticity, which can in turn guide future experiments (Froudist-Walsh et al, 2020;Kaiser, 2020). Going forward, non-human primate studies offer a unique method to investigate links between cellular and synaptic plasticity mechanisms after permanent lesions and subsequent large-scale changes to distributed brain network activity underlying higher cognitive functions.…”