The present results suggest that termino-terminal endogenous cholinergic activity controls DA release and that this involves activation of glutamate receptors in vitro. However, it is not known if promoting DA release by selective activation of CINs occurs in vivo. To test this possibility, FSCV recordings combined with optical stimulation from adjacent sites (200 μm separation) were performed by implantation of an optical fiber/carbon fiber arrangement (optrode, see Methods, Fig. 4A) into the NAc of urethane-anesthetized mice. Because under these recording conditions the recording electrode cannot be optimally placed in the area of highest fluorescence under visual control, the conditions necessary to obtain CIN-evoked release were different from those used in the slice. Optical stimulation was reliably achieved by delivery of a train of blue light (473 nm wavelength, 10 mW, 4 msec duration/pulse, 150 pulses, 20 Hz) through the optical fiber of the implanted optrode. Selective activation of accumbal CINs triggered a significant increase in DA concentration (18.2 ± 2.1 nM), respect to baseline values; n= 3) (Fig. 4B,C), providing unambiguous in vivo evidence that CIN activity locally enhances DA release in the NAc.
