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. 2015 Jan 21;40(6):1495–1509. doi: 10.1038/npp.2014.336

Figure 1.

Figure 1

Selective pattern of Cre recombinase expression and loss of D2 autoreceptors in autoDrd2KO mice. (a, b) Cre recombinase expression revealed with the fluorescent reporter tdTomato shown in coronal (a) and sagittal (b) brain sections of autoDrd2KO mice overlaid onto mouse brain atlas outline (Franklin and Paxinos, third edition, 2007). Note fluorescence in the ventral tegmental area (VTA), susbantia nigra compacta (SNC), and projections to the NAc and dorsal striatum (DS). In addition, Cre-expressing neurons were seen in the olfactory bulb (OB). SNR, substantia nigra reticulata; ml, medial lemniscus; ac, anterior commissure. Scale bars=1 mm. (c, d) Confocal images showing fluorescently labeled neuronal cell bodies in VTA (c) and axonal projection in the striatum (d). Scale bars=50 μm. (e) Channelrhodopsin-2 tagged eYFP expression in midbrain DA neurons and their axonal projections to NAc shell (NAcsh), core (NAcc), and dorsal striatum (DS) shown in sagittal brain section of autoDrd2 mice overlaid onto atlas outline. VP, ventral pallidum; LV, lateral ventricle; Tu, olfactory tubercle. (f, top) Representative eDA and oDA transients in NAc shell of autoDrd2KO mice. (f, bottom) Color plots showing voltammetric current (color scale) over time as a function of the applied potential (V). Inset shows current vs voltage plot of DA signals showing characteristic oxidation and reduction peaks. (g) Box-and-whisker plot of peak concentration for eDA and oDA transients recorded in control mice (open) and autoDrd2KO mice (solid): box=25–75 percentiles, whiskers=minimum–maximum, line=median, cross=mean. (h) Traces showing average oDA transients before and after application of the D2-like agonist quinpirole (1 μM, gray) and after subsequent application of the D2R antagonist sulpiride (1 μM, red) in control (top) and autoDRD2KO mice (bottom). (i) Quinpirole (1 μM) inhibit oDA transient in control mice (open), whereas it had no effect on autoDrd2KO (filled) mice. Sulpiride (1 μM) reversed the inhibition in control mice and had no effect on autoDrd2KO mice.