Figure 2
NRG1-mediated increases in extracellular DA requires direct ErbB4 signaling in DAergic neurons in vivo. Local delivery of NRG1 (left shaded area) and measurements of extracellular DA were performed using reverse microdialysis in the (a) dorsal hippocampus, (b) mPFC and (c) dorsal striatum of freely moving adult TH-Cre;ErbB4f/f (left, red lines) or PV-Cre;ErbB4f/f KO mice (right, green lines), and their corresponding ErbB4f/f littermate controls (black lines). Samples were collected for 15 min to account for low DA levels in the hippocampus and mPFC. Local ErbB4 activation with NRG1 (1 nm, 15 min) elicits a robust increase of extracellular DA in control ErbB4f/f mice (controls for TH-Cre;ErbB4f/f, hippocampus: 245.6±33.8%, n=6, mPFC: 208.9±19.2%, n=6, striatum: 179.7±9.1, n=6) (controls for PV-Cre;ErbB4f/f, hippocampus: 288.0±59.4%, n=6; mPFC: 193.6±8.5%, n=6, striatum: 166.1±6.0, n=6) and in PV-Cre;ErbB4f/f mutant mice (hippocampus: 328.2±71.0%, n=6, mPFC: 217.1±10.6%, n=6, striatum: 167.8±6.0%. n=6), but not in TH-Cre;ErbB4f/f mice (hippocampus: 94.8±8.7%, n=7, F(1,11)=11.73, P=0.0057; mPFC: 102.2±1.6%, n=6, F(1,10)=20.02, P=0.0012; striatum: 97.3±4.8%, n=6, F(1,10)=30.83, P=0.0002). The functionality of DA processes in each anatomical area was assayed 60 min after the NRG1 application when DA levels had returned to baseline by delivering a depolarizing KCl pulse (50 mm, 15 min). Extracellular DA levels increased in all genotypes, indicating that dopaminergic processes retained normal capacity for depolarization-dependent release. Data represent the mean±s.e.m. of the percentage of baseline variation. In c, DA increases in striatum during the KCl pulse were plotted on a second y axis shown on the right side of the graph. *P<0.05, **P<0.01 and ***P<0.005.
