The dysfunction of dopamine signaling can contribute to mood disorders and drug abuse. Dopamine neurons do not belong to one homogenous group and differ in their electrophysiological properties and molecular expression profiles. The midline dopamine neurons of the RLi and A10dc, which consists of the periaqueductal gray (PAG) and dorsal raphe, are particularly interesting because they project to brain regions that regulate anxiety and stress responsivity. We used a transgenic mouse line that expresses eGFP under control of the tyrosine hydroxylase (TH) promoter to explore the anatomy of dopamine neurons within the VTA, RLi, ventral PAG, and dorsal raphe. Retrograde tracer was injected into the dorsal bed nucleus of the stria terminals (BNST), a region important for stress-induced reinstatement of drug-seeking. As shown previously in rats, both A10dc and VTA dopamine neurons project to the dorsal BNST with the largest numbers of eGFP neurons labeled with tracer in the VTA, RLi, dorsal raphe and adjacent ventral PAG. The RLi neurons receive norepinephrine input, which may prime them for involvement in stress responses. Using the TH-eGFP mouse, we explored the physiology and noradrenergic modulation 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 did not persist following the subsequent application of prazosin and was therefore not a form of synaptic plasticity. Methoxamine increased the frequency of miniature EPSCs, indicating that the α1-AR action on glutamatergic transmission likely has a presynaptic mechanism. There was a modest decrease in sEPSC frequency with 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.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-07132015-103925 |
| Date | 20 July 2015 |
| Creators | Williams, Megan Ann |
| Contributors | Aurelio Galli, Ariel Deutch, David Bader, Danny Winder |
| Publisher | VANDERBILT |
| Source Sets | Vanderbilt University Theses |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.vanderbilt.edu/available/etd-07132015-103925/ |
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