Electrophysiological characterization of catecholamine-containing GFP-expressing dissociated mouse area postrema neurons and their response to glucagon-like peptide-1 receptor agonists

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Lee, Samantha
Fry, Mark
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The area postrema (AP) is a hindbrain sensory circumventricular organ that participates in energy balance regulation. Catecholamine-containing AP neurons are a key subpopulation that inhibit food intake and appear to mediate the appetite-reducing effects of glucagon-like peptide-1 (GLP-1) receptor agonists. Neither the electrophysiological properties nor the electrical response of CA-containing neurons to GLP-1 receptor agonists has been characterized. Therefore, we carried out patch clamp experiments on dissociated neuronal cultures from transgenic mice (TH-GFP). Voltage-clamp recordings revealed subtle differences in K+ current, Na+ current, and IH properties between TH and nonTH neurons. In current-clamp configuration, application of 1 μM GLP-1 or 1 μM Exendin-4 activated the majority of TH neurons tested. Our results suggest that TH neurons are an electrophysiologically heterogeneous population and confirm that GLP-1 receptor agonists activate most TH neurons. Together, it appears that TH neurons play multiple roles in integrating satiety information to ultimately reduce food intake.
Electrophysiology, GLP-1, Area postrema, Tyrosine hydroxylase