Impulse control suppresses actions that are inappropriate in one context, but may be beneficial in others. The medial prefrontal cortex (mPFC) mediates this process by providing a top-down signal to inhibit competing responses, although the mechanism by which the mPFC acquires this ability is unknown. To that end, we examined synaptic changes in the mPFC associated with learning to inhibit an incorrect response. Rats were trained in a simple response inhibition task to withhold responding until a signal was presented. We then measured synaptic plasticity of excitatory synapses in the mPFC, using whole-cell patch-clamp recordings, in brain slices prepared from trained rats. Response inhibition training significantly increased the relative contribution of AMPA receptors to the overall EPSC in prelimbic, but not infralimbic, neurons of the mPFC. This potentiation of synaptic transmission closely paralleled the acquisition and extinction of response inhibition. Using a retrograde fluorescent tracer, we observed that these plastic changes were selective for efferents projecting to the ventral striatum, but not the dorsal striatum or amygdala. Therefore, we suggest that response inhibition is encoded by a selective strengthening of a subset of corticostriatal projections, uncovering a synaptic mechanism of impulse control. This information could be exploited in therapeutic interventions for disorders of impulse control, such as addiction, attention deficit-hyperactivity disorder, and schizophrenia.

• 79277-1/CAPMC/ CIHR/Canada