Tuft dendrite spikes are accompanied by selective input from distinct functional networks

The tuft dendrites of layer 5 neurons can support regenerative events - dendritic spikes - that have been proposed to coordinate context-specific engagement and plasticity within cortical networks. However, it remains unclear whether tuft spikes are accompanied by input activity with dynamics that could support these network-level functions. To address this, glutamatergic synapses and postsynaptic calcium signals were simultaneously imaged in the tuft dendrites of layer 5 extratelencephalic neurons within the premotor cortex of mice of either sex performing a cued directional licking task. Trial-to-trial, the generation of tuft spikes was associated with a multiphasic elevation in synaptic activity spanning hundreds of milliseconds. This activity was highly specific to the dendrite in which a spike was detected, suggesting the concurrent activation of select subnetworks. Synapses that were strongly coupled to the overall population were the most synchronized with tuft spikes and preferentially encoded the transition between the preparation and action epochs of the task. Even among these strongly coupled synapses, increases in activity were largely specific to synapses located on the spiking dendrite. Surprisingly, among synapses with the poorest population coupling, a second population of coactive synapses was discovered that was also associated with tuft spikes and functionally selective for task-outcome. These results suggest that tuft spikes may be particularly driven by inputs from neurons that are both embedded in sparse subnetworks and synchronized through coupling to larger-scale functional networks.Significance Statement Flexible behavior and learning may depend on interactions between activity in different brain networks and dendritic spikes generated within the neurons that make up the output layer of the neocortex. The results of this study indicate that at the moment of spike generation, spikes in different dendrites are associated with the activation of very specific networks. Yet, across time, the inputs most associated with dendritic spikes are broadly coactive and share selectivity for similar features of behavior. This suggests that dendritic spikes may be particularly driven by the activation of "hub" neurons that coordinate communication between largescale and small-scale functional networks.