Activation of parvalbumin-expressing neurons reconfigures neuronal ensembles in murine striatal microcircuits

The striatum is the largest entrance to the basal ganglia. Diverse neuron classes make up striatal microcircuit activity, consisting in the sequential activation of neuronal ensembles. How different neuron classes participate in generating ensemble sequences is unknown. In control mus musculus brain slices in vitro, providing excitatory drive generates ensemble sequences. In Parkinsonian microcircuits captured by a highly recurrent ensemble, a cortical stimulus causes a transitory reconfiguration of neuronal groups alleviating Parkinsonism. Alternation between neuronal ensembles needs interconnectivity, in part due to interneurons, preferentially innervated by incoming afferents. One main class of interneuron expresses parvalbumin (PV+ neurons) and mediates feed-forward inhibition. However, its more global actions within the microcircuit are unknown. Using calcium imaging in ex vivo brain slices simultaneously recording dozens of neurons, we aimed to observe the actions of PV+ neurons within the striatal microcircuit. PV+ neurons in active microcircuits are 5%-11% of the active neurons even if, anatomically, they are <1% of the total neuronal population. In resting microcircuits, optogenetic activation of PV+ neurons turns on circuit activity by activating or disinhibiting, more neurons than those actually inhibited, showing that feed-forward inhibition is not their only function. Optostimulation of PV+ neurons in active microcircuits inhibits and activates different neuron sets, resulting in the reconfiguration of neuronal ensembles by changing their functional connections and ensemble membership, showing that neurons may belong to different ensembles at different situations. Our results show that PV+ neurons participate in the mechanisms that generate alternation of neuronal ensembles, therefore provoking ensemble sequences.