Mediodorsal thalamus contributes to the timing of instrumental actions

The ability to represent time in the brain relies on network interactions across multiple brain areas. While much attention has been paid to the role of prefrontal cortex and basal ganglia in timing, little work has been aimed towards understanding the role of the thalamus in timing. To this end, we utilized pharmacological and optogenetic techniques in mice to test the role of the mediodorsal nucleus of the thalamus (MD) in interval timing. The MD is strongly connected with the prefrontal cortex and receives major inputs from the basal ganglia output nuclei. We used an operant temporal production task, in which mice indicate their expected timing of available rewards by pressing a lever in anticipation. On probe trials, inactivation of the MD with muscimol produced rightward shifts in peak pressing as well as increases in peak spread, thus significantly altering both temporal accuracy and precision. Optogenetic inhibition of glutamatergic projection neurons in the MD resulted in similar changes in timing; the shift in peak time is proportional to the duration of inhibition. The observed effects were found to be independent of significant changes in movement. Taken together, these findings provide strong evidence for the import...Continue Reading