BDNF/TrkB signalling interacts with GABAergic system to inhibit rhythmic swallowing in the rat

Brain-derived neurotrophic factor (BDNF) acts as an anorexigenic factor in the dorsal vagal complex (DVC) of the adult rat brainstem. The DVC contains the premotoneurons controlling swallowing, a motor component of feeding behavior. Although rats with transected midbrain do not seek out food, they are able to swallow and to ingest food. Because BDNF and Tropomyosin-related kinase B receptors (TrkB) are expressed in the DVC, this study hypothetized that BDNF could modify the activity of premotoneurons involved in swallowing. Repetitive electrical stimulation of the superior laryngeal nerve (SLN) induces rhythmic swallowing that can be recorded using electromyographic electrodes inserted in sublingual muscles. We show that a microinjection of BDNF in the swallowing network induced a rapid, transient and dose-dependant inhibition of rhythmic swallowing. This BDNF effect appeared to be mediated via TrkB activation, since it no longer occurred when TrkB were antagonized by K252a. Interestingly, swallowing was inhibited when subthreshold doses of BDNF and GABA were coinjected, suggesting a synergistic interaction between these two signalling substances. Moreover, BDNF no longer had an inhibitory effect on swallowing when coinjected with bicuculline, a GABAA receptor antagonist. This blockade of BDNF inhibitory effect on swallowing was reversible, since it reappeared when BDNF was injected 15 minutes after bicuculline. Finally, we show that stimulation of SLN induced a decrease in BDNF protein within the DVC. Taken together, our results strongly suggest that BDNF inhibits swallowing via modulation of the GABAergic signalling within the central pattern generator of swallowing. BDNF, GABA, swallowing, medullary solitary tract nucleus; rat