Insulin Preferentially Regulates the Activity of Parasympathetic Preganglionic Neurons over Sympathetic Preganglionic Neurons

Background: Insulin is a peptide hormone that regulates post-prandial physiology, and it is well known that insulin controls homeo-stasis at least in part via the central nervous system. In particular, insulin alters the activity of neurons within the autonomic nervous system. However, currently available data are mostly from unidentified brainstem neurons of the dorsal motor nucleus of the vagus nerve (DMV).Methods: In this study, we used several genetically engineered mouse models to label distinct populations of neurons within the brainstem and the spinal cord for whole-cell patch clamp recordings and to assess several in vivo metabolic functions.Results: We first confirmed that insulin directly inhibited cholinergic (parasympathetic preganglionic) neurons in the DMV. We also found inhibitory effects of insulin on both the excitatory and inhibitory postsynaptic currents recorded in DMV cholinergic neurons. In addition, GABAergic neurons of the DMV and nucleus tractus solitarius were inhibited by insulin. However, insulin had no effects on the cholinergic sympathetic preganglionic neurons of the spinal cord. Finally, we obtained results suggesting that the insulin-induced inhibition of parasympathetic preganglionic neurons may not play a critical role in the regulation of glucose homeostasis and gastrointestinal motility.Conclusion: Our results demonstrate that insulin inhibits parasympathetic neuronal circuitry in the brainstem, while not affecting sympathetic neuronal activity in the spinal cord.