Excitatory drive onto dopaminergic neurons in the rostral linear nucleus is enhanced by norepinephrine in an α1 adrenergic receptor-dependent manner.

Williams MA, Li C, Kash TL, Matthews RT, Winder DG
Neuropharmacology. 2014 86: 116-24

PMID: 25018040 · PMCID: PMC4188726 · DOI:10.1016/j.neuropharm.2014.07.001

Dopaminergic innervation of the extended amygdala regulates anxiety-like behavior and stress responsivity. A portion of this dopamine input arises from dopamine neurons located in the ventral lateral periaqueductal gray (vlPAG) and rostral (RLi) and caudal linear nuclei of the raphe (CLi). These neurons receive substantial norepinephrine input, which may prime them for involvement in stress responses. Using a mouse line that expresses eGFP under control of the tyrosine hydroxylase promoter, we explored the physiology and responsiveness to norepinephrine of these neurons. We find that RLi dopamine neurons differ from VTA dopamine neurons with respect to membrane resistance, capacitance and the hyperpolarization-activated current, Ih. Further, we found that norepinephrine increased the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) on RLi dopamine neurons. This effect was mediated through the α1 adrenergic receptor (AR), as the actions of norepinephrine were mimicked by the α1-AR agonist methoxamine and blocked by the α1-AR antagonist prazosin. This action of norepinephrine on sEPSCs was transient, as it did not persist in the presence of prazosin. Methoxamine also increased the frequency of miniature EPSCs, indicating that the α1-AR action on glutamatergic transmission likely has a presynaptic mechanism. There was also a modest decrease in sEPSC frequency with the application of the α2-AR agonist UK-14,304. These studies illustrate a potential mechanism through which norepinephrine could recruit the activity of this population of dopaminergic neurons.

Copyright © 2014 Elsevier Ltd. All rights reserved.

MeSH Terms (20)

Animals Dopaminergic Neurons Electric Capacitance Electric Impedance Excitatory Postsynaptic Potentials Glutamic Acid Green Fluorescent Proteins Male Membrane Potentials Mice Mice, Inbred C57BL Mice, Transgenic Miniature Postsynaptic Potentials Norepinephrine Promoter Regions, Genetic Raphe Nuclei Receptors, Adrenergic, alpha-1 Receptors, Adrenergic, alpha-2 Tyrosine 3-Monooxygenase Ventral Tegmental Area

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