Norepinephrine inhibits Afferent activation of NTS Catecholamine Neurons in Mice

The nucleus tractus solitarius (NTS) integrates visceral sensory input to regulate feeding behavior, with catecholaminergic (CA) and neuropeptide Y (NPY)-expressing neurons playing key roles in energy homeostasis. Recent evidence suggests functional heterogeneity among CA-NTS neurons, including distinct subpopulations that either suppress or promote feeding. In this study, we investigated how norepinephrine (NE) modulates excitatory synaptic transmission from solitary tract (ST) afferents onto tyrosine hydroxylase-positive (TH⁺) NTS neurons in mice. Using patch-clamp electrophysiology in horizontal brainstem slices, we found that NE inhibits ST-evoked excitatory postsynaptic currents (ST-EPSCs) in a concentration-dependent manner, with maximal effects at ≥10 µM and an EC₅₀ of ∼3.4 µM. This inhibition was mediated by α₂-adrenergic receptors and was independent of GABA _A receptor activity. NE also suppressed asynchronous glutamate release and attenuated CCK-induced increase in spontaneous EPSC frequency, suggesting a presynaptic mechanism. NPY similarly reduced ST-EPSC amplitude via Y ₂ receptor activation, and co-application of NE and NPY produce additive or synergistic effects, even at subthreshold concentrations. Together, our results reveal a novel mechanism by which noradrenergic and peptidergic systems interact to regulate visceral sensory processing in the brainstem.

NTS