Differential attentional control mechanisms by two distinct noradrenergic coeruleo-frontal cortical pathways

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 117; no. 46; pp. 29080 - 29089
• Main Authors: Bari, Andrea, Xu, Sangyu, Pignatelli, Michele, Takeuchi, Daigo, Feng, Jiesi, Li, Yulong, Tonegawa, Susumu
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 17.11.2020
• Subjects: Animals; Attention; Attention - physiology; Biological Sciences; Brain - metabolism; Cognition - physiology; Cognitive ability; Frontal Lobe - drug effects; Frontal Lobe - metabolism; Impulsive behavior; Impulsive Behavior - physiology; Impulsivity; Inhibition (psychology); Inhibition, Psychological; Locus coeruleus; Locus Coeruleus - physiology; Mice; Mice, Transgenic; Neurons - metabolism; Norepinephrine; Norepinephrine - metabolism; Norepinephrine - pharmacology; Operant conditioning; Prefrontal cortex; Prefrontal Cortex - physiology; norepinephrine; attentional control; locus coeruleus; prefrontal cortex; response inhibition
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.2015635117

The attentional control of behavior is a higher-order cognitive function that operates through attention and response inhibition. The locus coeruleus (LC), the main source of norepinephrine in the brain, is considered to be involved in attentional control by modulating the neuronal activity of the prefrontal cortex (PFC). However, evidence for the causal role of LC activity in attentional control remains elusive. Here, by using behavioral and optogenetic techniques, we investigate the effect of LC neuron activation or inhibition in operant tests measuring attention and response inhibition (i.e., a measure of impulsive behavior). We show that LC neuron stimulation increases goal-directed attention and decreases impulsivity, while its suppression exacerbates distractibility and increases impulsive responding. Remarkably, we found that attention and response inhibition are under the control of two divergent projections emanating from the LC: one to the dorso-medial PFC and the other to the ventro-lateral orbitofrontal cortex, respectively. These findings are especially relevant for those pathological conditions characterized by attention deficits and elevated impulsivity.