The subdiaphragmatic vagus nerves mediate activation of locus coeruleus neurons by peripherally administered microbial substances

Our earlier studies demonstrated that representative microbial substances-lipopolysaccharide, peptidoglycan, and poly-inosine: poly-cytosine (poly(I):(C))-increased the spontaneous discharge rates and sensory-evoked responses of isolated locus coeruleus (LC) neurons in a dose- and time-related manner after i.p. injection into rats. We then turned our attention to the mechanism by which microbial substances administered into the peritoneal cavity affect the LC neurons. The involvement of the subdiaphragmatic vagus nerves was examined in this regard since several brain responses to peripherally administered lipopolysaccharide have been found to depend upon the integrity of these nerves. The experiments reported here show that lipopolysaccharide, peptidoglycan, and poly(I):(C) all failed to excite LC neurons after i.p. injection into rats that had previously been subjected to complete transection of the subdiaphragmatic vagus nerves. Furthermore, selective transection of the subdiaphragmatic vagus nerve trunks indicated that the dorsal trunk, and not the ventral trunk, was necessary to excite LC neurons in response to i.p. lipopolysaccharide. The inability of LC neurons to respond to i.p. lipopolysaccharide in vagotomized rats is unlikely to be attributed to a desensitization of the neurons to lipopolysaccharide since i.c.v. injection of lipopolysaccharide excited LC neurons in vagotomized rats as it did in vagus-intact rats. These findings suggest that a variety of microbial substances excited LC neurons after administration into the peritoneal cavity in a manner involving the subdiaphragmatic vagus nerves.