Distributed cell assemblies spanning prefrontal cortex and striatum

Highly synchronous neuronal assembly activity is deemed essential for cognitive brain function. In theory, such synchrony could coordinate multiple brain areas performing complementary processes. However, cell assemblies have been observed only in single structures, typically cortical areas, and little is known about their synchrony with downstream subcortical structures, such as the striatum. Here, we demonstrate distributed cell assemblies activated at high synchrony (∼10 ms) spanning prefrontal cortex and striatum. In addition to including neurons at different brain hierarchical levels, surprisingly, they synchronized functionally distinct limbic and associative sub-regions. These assembly activations occurred when members shifted their firing phase relative to ongoing 4 Hz and theta rhythms, in association with high gamma oscillations. This suggests that these rhythms could mediate the emergence of cross-structural assemblies. To test for the role of assemblies in behavior, we trained the rats to perform a task requiring cognitive flexibility, alternating between two different rules in a T-maze. Overall, assembly activations were correlated with task-relevant parameters, including impending choice, reward, rule, or rule order. Moreover, these behavioral correlates were more robustly expressed by assemblies than by their individual member neurons. Finally, to verify whether assemblies can be endogenously generated, we found that they were indeed spontaneously reactivated during sleep and quiet immobility. Thus, cell assemblies are a more general coding mechanism than previously envisioned, linking distributed neocortical and subcortical areas at high synchrony. •Neurons fire at high synchrony (∼10 ms) in prefrontal-striatal assemblies•For assembly activations, members phase lock to 4 and 8 Hz rhythms•Behavioral correlates are more robustly expressed by assemblies than their members•The assemblies are endogenously generated, spontaneously reactivating during rest Synchronous co-activations foster communication in cortical networks. Oberto et al. show very tight synchrony of prefrontal cortical and subcortical (striatal) neurons, coordinated by slow and fast brain rhythms. This leads to emergence of executive function-related behavioral correlates more robust than those expressed by the individual neurons.