Dynamic ErbB4 Activity in Hippocampal-Prefrontal Synchrony and Top-Down Attention in Rodents

• Published in: Neuron (Cambridge, Mass.) Mass.), 2018-04, Vol.98 (2), p.380-393.e4
• Main Authors: Tan, Zhibing, Robinson, Heath L., Yin, Dong-Min, Liu, Yu, Liu, Fang, Wang, Hongsheng, Lin, Thiri W., Xing, Guanglin, Gan, Lin, Xiong, Wen-Cheng, Mei, Lin
• Format: Article
• Language: English
• Subjects: ADHD; Attention deficit hyperactivity disorder; Bipolar disorder; Brain; E/I balance; ErbB-2 protein; ErbB4; GABA transmission; hippocampal-prefrontal synchrony; Hippocampus; Interneurons; Investigations; Kinases; major depression; Mental depression; Mental disorders; Neuregulin; Neuregulin 1; Neurons; Prefrontal cortex; Schizophrenia; Statistical analysis; top-down attention; γ-Aminobutyric acid
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/j.neuron.2018.03.018

Top-down attention is crucial for meaningful behaviors and impaired in various mental disorders. However, its underpinning regulatory mechanisms are poorly understood. We demonstrate that the hippocampal-prefrontal synchrony associates with levels of top-down attention. Both attention and synchrony are reduced in mutant mice of ErbB4, a receptor of neuregulin-1. We used chemical genetic and optogenetic approaches to inactivate ErbB4 kinase and ErbB4+ interneurons, respectively, both of which reduce gamma-aminobutyric acid (GABA) activity. Such inhibitions in the hippocampus impair both hippocampal-prefrontal synchrony and top-down attention, whereas those in the prefrontal cortex alter attention, but not synchrony. These observations identify a role of ErbB4-dependent GABA activity in the hippocampus in synchronizing the hippocampal-prefrontal pathway and demonstrate that acute, dynamic ErbB4 signaling is required to command top-down attention. Because both neuregulin-1 and ErbB4 are susceptibility genes of schizophrenia and major depression, our study contributes to a better understanding of these disorders. [Display omitted] •Hippocampal-prefrontal synchrony positively correlates with top-down attention level•Acute ErbB4 signaling regulates top-down attention•ErbB4-dependent GABA activity in hippocampus synchronizes PFC neurons in attention Top-down attention is important for cognitive function, but its underpinning mechanisms are not well understood. Tan et al. demonstrate that attention correlates with hippocampal-prefrontal synchrony, both of which require acute, dynamic activity of ErbB4.