RIKEN-MIT Laboratory for Neural Circuit Genetics, Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139;
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139.
Proc Natl Acad Sci U S A. 2020 Nov 17;117(46):29080-29089. doi: 10.1073/pnas.2015635117. Epub 2020 Nov 2.
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.
行为的注意力控制是一种通过注意力和反应抑制来运作的高级认知功能。蓝斑核(LC)被认为通过调节前额叶皮层(PFC)的神经元活动参与注意力控制,它是大脑中去甲肾上腺素的主要来源。然而,LC 活动在注意力控制中的因果作用的证据仍然难以捉摸。在这里,我们通过使用行为和光遗传学技术,在测量注意力和反应抑制的操作性测试(即冲动行为的度量)中研究 LC 神经元激活或抑制的效果。我们发现 LC 神经元的刺激增加了目标导向注意力并降低了冲动性,而其抑制则增加了分心并增加了冲动反应。值得注意的是,我们发现注意力和反应抑制受发自 LC 的两个发散投射的控制:一个投射到背内侧前额叶皮层,另一个投射到腹外侧眶额皮层。这些发现对于那些以注意力缺陷和冲动性升高为特征的病理状况尤其重要。