The interhemispheric amygdala-accumbens circuit encodes negative valence in mice

• Published in: Science (American Association for the Advancement of Science) 2024-11, Vol.386 (6722), p.eadp7520
• Main Authors: Tian, Zhen, Song, Jiachen, Zhao, Xuying, Zhou, Yiming, Chen, Xi, Le, Qiumin, Wang, Feifei, Ma, Lan, Liu, Xing
• Format: Article
• Language: English
• Subjects: Amygdala; Animals; Anterior commissure; Anterior Commissure, Brain - physiology; Anterior Commissure, Brain - ultrastructure; Avoidance; Avoidance behavior; Avoidance Learning; Axons; Basolateral Nuclear Complex - physiology; Basolateral Nuclear Complex - ultrastructure; Behavior; Brain; Brain commissures; Brain mapping; Calcium imaging; Cerebral hemispheres; Coding; Dopamine; Dopamine - metabolism; Dopamine D1 receptors; Dopamine D2 receptors; Emotional behavior; Escape behavior; Female; Forebrain; Gene sequencing; Genetics; Hemispheres; Historical structures; Information processing; Inhibition; Male; Mammals; Mice; Mice, Inbred C57BL; mRNA; Neural Pathways - physiology; Neural Pathways - ultrastructure; Neuroimaging; Neurons; Neurons - physiology; Nuclei; Nucleus accumbens; Nucleus Accumbens - cytology; Nucleus Accumbens - physiology; Nucleus Accumbens - ultrastructure; Optics; Phenotypes; Photometry; Physiology; Receptors, Dopamine D2 - metabolism; Reward; Spiny neurons; Stimuli; Stria terminalis; Symmetry; Tracing; Vertebrates
• ISSN: 0036-8075; 1095-9203; 1095-9203
• DOI: 10.1126/science.adp7520

The structurally symmetric mammalian brain hemispheres are interconnected by commissural axons across the midline. However, the functions of interhemispheric connectivity remain largely unknown. We found that in mice, transection of the anterior commissure (AC), which connects the rostroventral forebrain, impaired avoidant behaviors. The basolateral amygdala (BLA) in the mouse projects to the contralateral nucleus accumbens (NAc) through the AC, independent of its ipsilateral projections. Aversive stimuli activated contralateral BLA-NAc projections. Positive stimuli, however, activated ipsilateral projections. Selective activation of contralateral BLA-NAc projections activated D2-positive medium spiny neurons (D2-MSNs), reduced NAc dopamine levels, and caused aversion, whereas selective activation of ipsilateral BLA-NAc projections activated D1-MSNs, increased NAc dopamine levels, and induced reward. The contralateral BLA-AC-NAc pathway is crucial for encoding negative valence, demonstrating distinct functions of intra- and interhemispheric circuits in brain physiology.