The Parafascicular Role in Updating Action from a Spatial to a Visual Strategy is Driven by its Glutamatergic Mesencephalic Locomotor Region inputs

The ability to update actions depends on the thalamus's parafascicular nucleus (PF); however, which PF's inputs control this function is unknown. Here, using fiber-photometry, retrograde labeling, ex-vivo electrophysiology, and optogenetic manipulations, we identify the contribution of the PF and its glutamatergic inputs to the update from a spatial to a visually guided strategy in a set-shifting task conducted in mice (of either sex). Our results show 1) GCaMP signals from the PF recorded along the update from a spatial to a visual strategy correlate with the probability of selecting the correct action based on a light stimulus. 2) Optogenetic inhibition of the PF during this update decreases the probability of selecting the correct action. 3) The mesencephalic locomotor region (MLR) was found to have the highest probability of synaptic connections with the PF. 4) GCaMP recordings from the MLR→PF input support it as a main driver in allowing the PF update function. 5) Inhibition of the MLR→PF connection decreases the probability of updating the contingency. These findings identify the inputs from the MLR as a crucial driver of the PF's role in controlling the update of actions.<b>Significance Statement</b> The information reaching the parafascicular nucleus (PF) and contributing to its role in contingency updating has not been thoroughly explored. Our study revealed the role of the glutamatergic inputs from the locomotor mesencephalic region (MLR) in the utilization of a visual stimulus for the rule-switching function of this nucleus. We recorded and inhibited the activity reaching the PF from different inputs and established that main driver of the PF's activity is the MLR glutamatergic input, undercovering a non-motor function of this area.