Abstract
SUMMARYDopamine is required for working memory, but how it modulates the large-scale cortex is unknown. Here, we report that dopamine receptor density per neuron, measured by autoradiography, displays a macroscopic gradient along the macaque cortical hierarchy. This gradient is incorporated in a connectome-based large-scale cortex model endowed with multiple neuron types. The model captures an inverted U-shaped dependence of working memory on dopamine and spatial patterns of persistent activity observed in over 90 experimental studies. Moreover, we show that dopamine is crucial for filtering out irrelevant stimuli by enhancing inhibition from dendrite-targeting interneurons. Our model revealed that an activity-silent memory trace can be realized by facilitation of inter-areal connections and that adjusting cortical dopamine induces a switch from this internal memory state to distributed persistent activity. Our work represents a cross-level understanding from molecules and cell types to recurrent circuit dynamics underlying a core cognitive function distributed across the primate cortex.
Highlights
Our ability to think through difficult problems without distraction is a hallmark of cognition
We estimated the cortical hierarchy using laminar connectivity data (Figure 1D, ii; STAR Methods; Markov et al, 2014a), expanding previous descriptions of the cortical hierarchy based on fewer regions (Markov et al, 2014a; Mejias et al, 2016)
Because we have connectivity data for two distinct sensory modalities, we calculated a circular embedding of the connectivity data, with radial distance from the edge representing the hierarchical position and angular distance between points representing the inverse of their connectivity strength (Chaudhuri et al, 2015)
Summary
Our ability to think through difficult problems without distraction is a hallmark of cognition. When at the supermarket looking for your favorite butter, it is important to keep in mind its distinctive golden packaging and not be distracted by the many other dairy products. This brain function is called working memory. Working memory often engages persistent neural activity that is specific to the information that must be remembered This mnemonic activity is sustained internally across multiple cortical and subcortical areas in the absence of external stimulation (Funahashi et al, 1989; Fuster and Alexander, 1971; Guo et al, 2017; Leavitt et al, 2017; Mejias and Wang, 2021; Mendoza-Halliday et al, 2014; Murray et al, 2017; Romo et al, 1999; Romo and Salinas, 2003; Vergara et al, 2016; Wang, 2001; Zhang et al, 2019)
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