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1 Vollum Institute, Oregon Health Sciences University, Portland, Oregon, United States; Vollum Institute, Oregon Health Sciences Univ, Portland, Oregon, United States
2 Vollum Institute, Oregon Health Sciences Univ, Portland, Oregon, United States
* To whom correspondence should be addressed. E-mail: westbroo{at}ohsu.edu.
Most central neurons package and release a single transmitter. However co-transmission of fast-acting and modulatory transmitters has been observed in vertebrate and invertebrate systems. Here, we describe a population of periglomerular cells in mouse brain slices (PND14-21) that co-release dopamine and GABA. We made whole-cell recordings from periglomerular cells that expressed EGFP under the control of the tyrosine hyrdoxylase (TH) promoter. Immunolabeling confirmed that EGFP+ periglomerular cells synthesized TH as well as glutamic acid decarboxylase (GAD). Stimulation of ORN afferent input evoked EPSCs in EGFP+ cells that were inhibited by cocaine, which blocks dopamine transport. These effects were reversed by the D2 receptor antagonist sulpiride. Cocaine also increased the paired-pulse ratio of ORN-evoked EPSCs. These results demonstrate that TH+ periglomerular cells spontaneously release dopamine. In addition to dopamine, TH-EGFP+ cells also released GABA. Brief depolarizing voltage-steps in labeled cells evoked a tail current that was completely blocked by the GABAA receptor antagonist gabazine and by cadmium, indicative of calcium-dependent self-inhibition in periglomerular cells (Smith and Jahr, 2002). However, similar voltage steps were insufficient to cause D2-receptor mediated inhibition of ORN terminals. Our results indicate that TH+ periglomerular cells are directly activated by ORN input and release both dopamine and GABA. We suggest that concerted activation of multiple periglomerular cells may be required to detect dopamine release under normal physiological conditions.
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