Abstract
Background & aims:
Chronic constipation has attracted considerable attention because of its negative impact on quality of life. Although defecation depends on local anorectal motility coordinated by the central nervous system, how it is regulated by the brain remains unclear.
Methods:
Brain areas responsible for defecation, known as the defecation brain area (DBA), were identified using a trans-synaptic tracing virus, pseudorabies virus (PRV). Candidate DBAs were assessed using opto- and chemogenetic methods and in vivo monitoring of neural activity.
Results:
A significant number of PRV-infected cells were observed in the Barrington's nucleus (Bar), locus coeruleus (LC), ventrolateral periaqueductal gray (vlPAG), and paraventricular hypothalamic nucleus (PVH) following virus infection in the distal colon. Opto- and chemogenetic activation studies revealed that vesicular glutamate transporter 2 (VGluT2) neurons in the Bar and LC, and corticotropin-releasing hormone (CRH) neurons in the Bar exhibit prompt (short-acting) and delayed (long-lasting) contractions in the distal colon, respectively. Their neural activities increased and peaked during spontaneous defecation. In contrast, activation of tyrosine hydroxylase neurons in the LC, which co-express VGluT2, exhibited no response. PRV experiments revealed that PVHVGluT2 and vlPAGCRH neurons are upstream neurons that connect to BarVGluT2 neurons, and their optogenetic activation resulted in a contraction of the distal colon.
Conclusions:
The study is the first to show that the Bar works as the pontine DBA, where BarVGluT2 and BarCRH neurons exert prompt and delayed defecation activity, respectively. PVHVGluT2 and vlPAGCRH neurons are candidates for upstream neurons that regulate defecation through BarVGluT2 neurons.
Keywords:
Chronic Constipation; Defecation; Defecation Brain Area.