Cortically induced heterosynaptic suppression of HP responses in the VS does not involve CB1 receptor activation. A, Averaged EPSP amplitudes for individual MSNs treated with AM251 (2 μm) showing that HP2 EPSPs are significantly reduced compared with HP1 responses evoked at a similar membrane potential. Inset, Averaged depolarized HP1 and basal HP2 EPSPs in the same representative cell. B, Plot comparing the magnitude of HP2 suppression driven by PFC stimulation under baseline conditions and in the presence of AM251 for individual MSNs. No change in suppression was observed following blockade of CB1 receptors. C, Responses to optogenetic stimulation of HP terminals before (HP1) and 50 ms after (HP2) PFC train stimulation in a representative MSN treated with AM251. Averaged responses to HP1 and HP2 (highlighted in red and blue, respectively) are overlaid in the inset (average of 15 sweeps; gray). *p < 0.05.