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Neocortical choline acetyltransferase (ChAT)-expressing interneurons are a subclass of vasoactive intestinal peptide (ChAT-VIP) neurons of which circuit and behavioural function are unknown. Here, we show that ChAT-VIP neurons directly excite neighbouring neurons in several layers through fast synaptic transmission of acetylcholine (ACh) in rodent medial prefrontal cortex (mPFC). Both interneurons in layers (L)1-3 as well as pyramidal neurons in L2/3 and L6 receive direct inputs from ChAT-VIP neurons mediated by fast cholinergic transmission. A fraction (10-20%) of postsynaptic neurons that received cholinergic input from ChAT-VIP interneurons also received GABAergic input from these neurons. In contrast to regular VIP interneurons, ChAT-VIP neurons did not disinhibit pyramidal neurons. Finally, we show that activity of these neurons is relevant for behaviour and they control attention behaviour distinctly from basal forebrain ACh inputs. Thus, ChAT-VIP neurons are a local source of cortical ACh that directly excite neurons throughout cortical layers and contribute to attention.

Attending the sensory environment for cue detection is a cognitive operation that occurs on a time scale of seconds. The dorsal and ventral medial prefrontal cortex (mPFC) contribute to separate aspects of attentional processing. Pyramidal neurons in different parts of the mPFC are active during cognitive behavior, yet whether this activity is causally underlying attentional processing is not known. We aimed to determine the precise temporal requirements for activation of the mPFC subregions during the seconds prior to cue detection. To test this, we used optogenetic silencing of dorsal or ventral mPFC pyramidal neurons at defined time windows during a sustained attentional state. We find that the requirement of ventral mPFC pyramidal neuron activity is strictly time-locked to stimulus detection. Inhibiting the ventral mPFC 2 s before or during cue presentation reduces response accuracy and hampers behavioral inhibition. The requirement for dorsal mPFC activity on the other hand is temporally more loosely related to a preparatory attentional state, and short lapses in pyramidal neuron activity in dorsal mPFC do not affect performance. This only occurs when the dorsal mPFC is inhibited during the entire preparatory period. Together, our results reveal that a dissociable temporal recruitment of ventral and dorsal mPFC is required during attentional processing.

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]