Optogenetic inhibition of this pathway attenuated this behavior, while optogenetic stimulation enhanced it. These data demonstrate that activity in vHipp axons in the NAc drive cocaine-induced locomotion, and the context dependence of this behavior might be attributable to activity in this pathway (Badiani et al., 2011; Vezina and Leyton, 2009). Since neither activation

nor inactivation of this pathway influenced basal locomotion, the differential effects after cocaine injections PF-01367338 price are presumably related to drug-induced dopamine signaling. Dopamine may bias postsynaptic activity toward one cell type or another and interactions with glutamate probably control the extent of cocaine-induced locomotion. These findings contradict the idea that a decrease in NAc neuron excitability promotes cocaine-induced locomotion (Dong et al., 2006) but are consistent with evidence that striatal c-fos induction is much stronger if cocaine injections are given in a novel environment ( Uslaner et al., 2001). The impact of attenuating vHipp input on cocaine-induced locomotion grew over repeated injections, which raises the possibility that vHipp-induced locomotion during cocaine use is related to behavioral sensitization buy GPCR Compound Library to cocaine. Overall, however,

the sensitizing effect of repeated cocaine injections was observed in spite of the optogenetic manipulations. The most notable finding presented here might be that photostimulation of each of the different afferent pathways to the NAc reinforced instrumental behavior. Admittedly, the bulk stimulations used were not physiological, but the fact that activity in each pathway can support these behaviors is a critical characteristic of the network. It highlights the similarities of these inputs and raises the possibility that the specific pathway releasing glutamate is not as important as the amount of glutamate that is released. Additionally, the information encoded in these inputs clearly has motivational value, which supports the theory that dopamine in the NAc acts to amplify or regulate the incentive properties of environmental stimuli that are presumably encoded in glutamatergic

signals (Berridge, 2007). Ventral tegmental area dopamine neurons innervate the NAc, and similar behaviors have been observed Acesulfame Potassium when these neurons are selectively stimulated (Witten et al., 2011). A challenge now is in determining when each glutamatergic pathway is physiologically active and consequential in shaping behavior. Potential confounds of the in vivo ChR2 data include the back propagation of ChR2-induced action potentials as well as activation of fibers that simply pass through the illuminated region of the brain. With our optical equipment, photostimulation could have occurred in the NAc as well as more medial nuclei, including the intermediate lateral septal nucleus and the nucleus of the vertical limb of the diagonal band.