W220 - Gamma-delta T Cells Suppress Microbial Metabolites That Activate Striatal Neurons and Induce Repetitive/compulsive Behavior

Laura Cox – Assistant Professor, Neurology, Brigham and Women's Hospital; Julia Mayrink – Postoctoral fellow, Neurology, Brigham and Women's Hospital; Danielle LeServe – Research Assistant, Neurology; Lydia Guo; Marilia Oliveira – Postoctoral fellow, Neurology, Brigham and Women's Hospital; Roberta Fonseca – Postoctoral fellow, Neurology, Brigham and Women's Hospital; Bruna Tatematsu; Luisa Lemos; Eduardo Lobo; Thais Moreira – Instructor, Neurology, Brigham and Women's Hospital; Andre Oliveira; Howard Weiner – Professor, Neurology, Brigham and Women's Hospital

Abstract Text: Intestinal gamma-delta (gd) T cells play an important role in shaping the gut microbiota, which is critical not only for maintaining intestinal homeostasis but also for controlling brain function and behavior. Here, we found that mice deficient for gd T cells (gd-/-) developed an abnormal pattern of repetitive/compulsive behavior, which was dependent on the gut microbiota. Colonization of WT mice with gd-/- microbiota induced repetitive/compulsive behavior whereas colonization of gd-/- mice with WT microbiota abolished the repetitive/compulsive behavior. Moreover, gd-/- mice had elevated levels of the microbial metabolite 3-phenylpropanoic acid in their cecum, which is a precursor to hippurate (HIP). HIP reaches the striatum and abnormally activates dopamine type 1 (D1R)-expressing medium spiny neurons, leading to repetitive/compulsive behavior. Altogether, these data suggest that intestinal gd T cells shape the gut microbiota and their metabolites and prevent dysfunctions of the striatum associated with behavior modulation.