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A neural pathway from prefrontal cortex (PFC) to dorsal striatum (DS) has been suggested to mediate cognitive control of behavior, including proactive inhibitory control and attention. However, a direct causal demonstration thereof is lacking. Here, we show that selective chemogenetic silencing of corticostriatal PFC neurons in rats increases premature responses. Wireless single-unit electrophysiological recordings of optogenetically identified corticostriatal PFC neurons revealed that the majority of these neurons encode behavioral trial outcome with persistent changes in firing rate. Attentional parameters were not affected by silencing corticostriatal PFC neurons, suggesting that these projection neurons encode a specific subset of cognitive behaviors. Compared to the general non-identified neuronal population in the PFC, frontostriatal neurons showed selective engagement during periods of inhibitory control. Our results demonstrate a role for corticostriatal neurons in inhibitory control and possibly suggest that distinct domains of cognitive control over behavior are encoded by specific projection neuron populations. • Silencing of dorsal frontostriatal projection neurons impairs behavioral inhibition • Frontostriatal neurons are predominantly persistently activated or silenced • Frontostriatal neurons show selective activity dynamics within the mPFC • Activity of frontostriatal neurons is related to behavioral control Terra et al. investigate the role of dorsal mPFC-to-medial dorsal striatum projection neurons in behavioral inhibition. Chemogenetic silencing of frontostriatal neurons results in a loss of behavioral inhibition. Within the mPFC, frontostriatal neurons selectively show persistent changes in activity, related to successful behavioral inhibition. [ABSTRACT FROM AUTHOR]