Figure 6.

Changes in VP_VGluT2 synapses after cocaine CPP and abstinence. A, System level. Drawings are arranged such that synapses on aversive targets are on top (VP_VGluT2, LHb, VTA_GABA) and synapses on rewarding (VP_GABA, VTA_DA) or neutral (MDT) targets are at the bottom. Left, Saline mice. VP_VGluT2 neurons make the strongest synapses on each other and on LHb neurons. Right, After cocaine CPP and abstinence. The synapses of VP_VGluT2 neurons on LHb and VTA_GABA are strengthened, whereas synapses on all rewarding targets are weakened. The synapse on MDT does not seem to change. B, Hypothesized synaptic mechanisms. Top, Saline. Bottom, After cocaine CPP and abstinence. Width of arrows at their bases and ends reflects the strength of the synapse in control and after abstinence, respectively. Saline mice, VP_VGluT2 synapses on each other and on LHb neurons show the highest number of AMPA receptors (based on highest AMPA/NMDA ratios) compared with the inputs to the VTA, MDT, and VP_GABA neurons. Presynaptic parameters (represented in the drawing by the number of vesicles in the terminal) are similar between synapses. After abstinence, synapses on aversive targets (except VP_VGluT2 neurons) are potentiated, either presynaptically (VTA_GABA) or both presynaptically and postsynaptically (LHb). Synapses on other VP_VGluT2 neurons seem to weaken. All synapses on reward targets are depressed through a postsynaptic mechanism (fewer postsynaptic AMPA receptors).