Dopamine D1 receptor expression in prefrontal parvalbumin neurons influences distractibility across species

Kavli Affiliate: Anirvan Nandy

| Authors: Mary Kate P Joyce, Tsvetoslav G Ivanov, Fenna Krienen, Jude Mitchell, Shaojie Ma, Wataru Inoue, Anirvan P Nandy, Dibyadeep Datta, Alvaro Duque, Jon I Arellano, Rahul Gupta, Guillermo Gonzalez-Burgos, David A Lewis, Nenad Sestan, Steven A McCarroll, Julio C Martinez-Trujillo, Seán Froudist-Walsh and Amy FT Arnsten

| Summary:

Marmosets and macaques are common non-human primate models of cognition, yet marmosets appear more distractible and perform worse in cognitive tasks. The dorsolateral prefrontal cortex (dlPFC) is pivotal for sustained attention, and prior macaque research suggests that dopaminergic modulation and inhibitory parvalbumin (PV) neurons could contribute to distractibility. Thus, we compared the two species using a visual fixation task with distractors, performed molecular and anatomical analyses in dlPFC, and linked functional microcircuitry with cognitive performance using computational modeling. We found that marmosets are more distractible than macaques, and that marmoset dlPFC PV neurons contain higher levels of dopamine-1 receptor (D1R) transcripts and protein, similar to their levels in mice. The modeling indicated that higher D1R expression in marmoset dlPFC PV neurons may increase distractibility by making dlPFC microcircuits more vulnerable to disruptions of their task-related persistent activity, especially when dopamine is released in dlPFC in response to unexpected salient stimuli.

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