A dopamine gradient controls access to distributed working memory in the large-scale monkey cortex

Area of Science:

• Neuroscience
• Cognitive Science
• Computational Neuroscience

Background:

• Dopamine is essential for working memory.
• The precise mechanisms by which dopamine modulates large-scale cortical networks for working memory remain unclear.

Purpose of the Study:

• To investigate the macroscopic gradient of dopamine receptor density in the primate cortex.
• To model how dopamine influences working memory and cortical activity patterns.
• To understand dopamine's role in stimulus filtering and memory trace mechanisms.

Main Methods:

• Autoradiography to measure dopamine receptor density per neuron.
• Development of a connectome-based large-scale cortical model with multiple neuron types.
• Simulations to capture working memory dynamics and persistent activity.

Main Results:

• A macroscopic gradient of dopamine receptor density was observed along the macaque cortical hierarchy.
• The model replicated the inverted U-shaped relationship between dopamine levels and working memory capacity.
• Dopamine enhances inhibition via dendrite-targeting interneurons, crucial for filtering irrelevant stimuli.
• The model demonstrated how dopamine facilitates activity-silent memory traces and switches between memory states.

Conclusions:

• Dopamine receptor density exhibits a gradient across the cortical hierarchy, influencing working memory.
• Dopamine plays a critical role in cognitive control, including working memory and stimulus filtering.
• The study provides a cross-level understanding of dopamine's molecular and cellular effects on large-scale cortical dynamics for cognition.