Slice Preparation and Electrophysiology.

Coronal slices (300 µm) containing the NAc were prepared as previously described (38). Recordings were performed using the MultiClamp 700B/Digidata 1550A System (Molecular Devices) digitized at a 10,000-Hz sampling frequency. All of the electrophysiological recordings were analyzed using Clampfit 10.9 software (Molecular Devices). Only cells with a stable resting membrane potential negative to −80 mV, overshooting action potentials (exceeding 75 to 80 mV threshold to peak), and an input resistance >80 MΩ were included. Furthermore, cells were rejected if resting membrane potential and input resistance changed more than 20%.

Excitatory postsynaptic potentials were recorded in whole-cell, current-clamp mode from NAc MSNs. Baseline EPSPs were recorded for 10 min at 0.2-Hz stimulation. To generate synaptic plasticity, we paired a single postsynaptic action potential elicited by brief somatic current injections (1 nA; 1 to 2 ms) and electrically driven EPSPs. In particular, a post-before-pre pairing protocol (Δt = −20 ms) was applied 90 times at 1 Hz. Inhibitory inputs were not blocked using GABA_A blockers. The change in EPSP slope was evaluated 35 to 40 min after the end of the pairing period and normalized to the baseline EPSP slope. The EPSP slope was measured as a linear fit between time points on the rising phase of the EPSP corresponding to 25 and 75% of the peak amplitude during control conditions. A more detailed description of the methodologies used in both current- and voltage-clamp recordings can be found in SI Appendix.