Sensory information from the gastrointestinal (GI) tract is transmitted centrally via primary afferents that terminate within the nucleus of the tractus solitarius (NTS) and utilize glutamate as their major neurotransmitter. Neurons of the NTS integrate this sensory information and transmit it to parasympathetic preganglionic neurons of the dorsal motor nucleus of the vagus (DMV), as well as to other areas, using principally glutamate, GABA and norepinephrine as neurotransmitters. Although susceptible to modulation by a vast array of neurotransmitters, the glutamatergic NTS to DMV synapse seems to play a minor role in the tonic modulation of gastric vagal reflexes. GABAergic neurotransmission between the NTS and DMV, however, is of critical importance as its in vivo blockade induces dramatic effects on gastric tone, motility and secretion. In in vitro experiments, however, this synapse appears initially resistant to modulation by most exogenously applied neuromodulators. Using opioid peptides as a model, this review will discuss the remarkable plasticity of the NTS-DMV GABAergic synapse. Modulation of this synapse appears dependent upon the levels of cAMP within the brainstem circuit. In particular, this review will outline how vagal afferent inputs appear to dampen the cAMP-PKA system via tonic activation of metabotropic glutamate receptors. Removal of vagal sensory input, coincident activation of the cAMP-PKA system, or inhibition of group II metabotropic glutamate receptors, allows receptor trafficking to occur selectively at the level of the NTS-DMV GABAergic synapse. Thus, we propose that the state of activation of vagal sensory inputs determines the gastric motor response via selective engagement of GABAergic synapses. This mini-review is based upon a presentation given at the International Society for Autonomic Neuroscience meeting in Marseille, France in July 2005.