Adrenoreceptor Modulation 1 2 3 4 5 6 7 8 9 Adrenoreceptor Modulation of Oromotor Pathways in the Rat Medulla

43 44 45 Regulation of feeding behavior involves the integration of multiple physiologic and 46 neurologic pathways that control both nutrient seeking and consummatory behaviors. The 47 consummatory phase of ingestion includes stereotyped oromotor movements of the tongue 48 and jaw that are controlled through brainstem pathways. These pathways not only 49 encompass cranial nerve sensory and motor nuclei for processing feeding-related afferent 50 signals and supplying the oromotor musculature, but also reticular neurons for 51 orchestrating ingestion and coordinating it with other behaviors that utilize the same 52 musculature. Based on decerebrate studies, this circuit should be sensitive to satiety 53 mechanisms mediated centrally by A2 noradrenergic neurons in the caudal nucleus of the 54 solitary tract (cNST) that are potently activated during satiety. Because the first observable 55 phase of satiety is inhibition of oromotor movements, we hypothesized that 56 norepinephrine (NE) would act to inhibit pre-hypoglossal neurons in the medullary 57 reticular formation. Using patch clamp electrophysiology of retrogradely labeled pre58 hypoglossal neurons and calcium imaging to test this hypothesis, we demonstrate that 59 norepinephrine can influence both preand postsynaptic properties of reticular neurons 60 through both 1and 2-adrenoreceptors. The 1-adrenoreceptor agonist phenylephrine 61 (PE) activated an inward current in the presence of TTX, and increased the frequency of 62 both inhibitory and excitatory miniature postsynaptic currents. The 2-adrenoreceptor 63 agonist dexmedetomidine (DMT) inhibited caudal NST-evoked excitatory currents as well 64 as spontaneous and miniature excitatory currents through presynaptic mechanisms. The 65 diversity of adrenoreceptor modulation of these pre-hypoglossal neurons may reflect their 66 role in a multifunctional circuit coordinating both ingestive and respiratory lingual 67 function. 68 69