ena-STUDY-FUNCTIONAL GENOMICS CENTER ZURICH-16-03-2017-10:48:19:685-231
Abdominal Vagal Afferents Modulate the Brain Transcriptome and Behaviors Relevant to Schizophrenia
Reduced activity of vagal efferents has long been implicated in schizophrenia and appears to be responsible for diminished parasympathetic activity and associated peripheral symptoms in affected individuals. In contrast, only little attention has been paid to the possibility that impaired afferent vagal signaling may be relevant for the disorder's pathophysiology as well. The present study explored this hypothesis using a rat model of subdiaphragmatic vagal deafferentation (SDA), which is the most complete and selective vagal deafferentation method existing to date. Using next-generation mRNA sequencing, we show that SDA leads to brain transcriptional changes in functional networks annotating with schizophrenia. We further demonstrate that SDA induces a hyperdopaminergic state, which is manifest as increased sensitivity to acute amphetamine treatment and elevated levels of dopamine in the nucleus accumbens. Our study also shows that SDA impairs sensorimotor gating and the attentional control of associative learning, which were assessed using the paradigms of prepulse inhibition and latent inhibition, respectively. These data provide converging evidence suggesting that various schizophrenia-related functions are subjected to visceral modulation through abdominal vagal afferents. Hence, afferent visceral signals may have a key role in shaping transcriptional, neurochemical and behavioral dysfunctions relevant to schizophrenia and related psychotic disorders.
Reduced activity of vagal efferents has long been implicated in schizophrenia and appears to be responsible for diminished parasympathetic activity and associated peripheral symptoms in affected individuals. In contrast, only little attention has been paid to the possibility that impaired afferent vagal signaling may be relevant for the disorder's pathophysiology as well. The present study explored this hypothesis using a rat model of subdiaphragmatic vagal deafferentation (SDA), which is the most complete and selective vagal deafferentation method existing to date. Using next-generation mRNA sequencing, we show that SDA leads to brain transcriptional changes in functional networks annotating with schizophrenia. We further demonstrate that SDA induces a hyperdopaminergic state, which is manifest as increased sensitivity to acute amphetamine treatment and elevated levels of dopamine in the nucleus accumbens. Our study also shows that SDA impairs sensorimotor gating and the attentional control of associative learning, which were assessed using the paradigms of prepulse inhibition and latent inhibition, respectively. These data provide converging evidence suggesting that various schizophrenia-related functions are subjected to visceral modulation through abdominal vagal afferents. Hence, afferent visceral signals may have a key role in shaping transcriptional, neurochemical and behavioral dysfunctions relevant to schizophrenia and related psychotic disorders.