title: Excitatory drive onto dopaminergic neurons in the rostral linear nucleus is enhanced by norepinephrine in an α1 adrenergic receptor-dependent manner.
abstract: 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.
authors.affiliation: Vanderbilt Brain Institute, Vanderbilt University School of Medicine, Nashville TN 37232, USA; Neuroscience Program in Substance Abuse, Vanderbilt University School of Medicine, Nashville TN 37232, USA. Electronic address: megan.a.fettig@vanderbilt.edu.
authors.forename: Megan A
authors.initials: MA
authors.lastname: Williams
authors.affiliation: Curriculum in Neuroscience, School of Medicine, University of North Carolina-Chapel Hill, Chapel Hill, NC 27599, USA; Bowles Center for Alcohol Studies, School of Medicine, University of North Carolina-Chapel Hill, Chapel Hill, NC 27599, USA. Electronic address: chia.li@nih.gov.
authors.forename: Chia
authors.initials: C
authors.lastname: Li
authors.affiliation: Bowles Center for Alcohol Studies, School of Medicine, University of North Carolina-Chapel Hill, Chapel Hill, NC 27599, USA; Department of Pharmacology, School of Medicine, University of North Carolina-Chapel Hill, Chapel Hill, NC 27599, USA. Electronic address: thomas_kash@med.unc.edu.
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Kash
authors.affiliation: Department of Molecular Physiology & Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232, USA. Electronic address: robert.matthews@vanderbilt.edu.
authors.forename: Robert T
authors.initials: RT
authors.lastname: Matthews
authors.affiliation: Vanderbilt Brain Institute, Vanderbilt University School of Medicine, Nashville TN 37232, USA; Neuroscience Program in Substance Abuse, Vanderbilt University School of Medicine, Nashville TN 37232, USA; Department of Molecular Physiology & Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232, USA; Kennedy Center for Research on Human Development, Vanderbilt University School of Medicine, Nashville, TN 37232, USA. Electronic address: danny.winder@vanderbilt.edu.
authors.forename: Danny G
authors.initials: DG
authors.lastname: Winder
mesh_terms: D000818:Animals; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000502:physiology*; D025802:Electric Capacitance; D017097:Electric Impedance; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D055369:Miniature Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D009638:Norepinephrine / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011903:Raphe Nuclei / Q000187:drug effects / Q000502:physiology*; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000502:physiology
chemical_list: D018340:Receptors, Adrenergic, alpha-1; D018341:Receptors, Adrenergic, alpha-2; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D018698:Glutamic Acid; D014446:Tyrosine 3-Monooxygenase; D009638:Norepinephrine
keywords: Dopamine; Excitatory transmission; Extended amygdala; Norepinephrine; Rostral linear nucleus