Thalamic regulation of switching between cortical representations enables cognitive flexibility
Interactions between the prefrontal cortex (PFC) and mediodorsal thalamus are critical for cognitive flexibility, yet the underlying computations are unknown. To investigate frontothalamic substrates of cognitive flexibility, we developed a behavioral task in which mice switched between different sets of learned cues that guided attention toward either visual or auditory targets. We found that PFC responses reflected both the individual cues and their meaning as task rules, indicating a hierarchical cue to rule transformation. Conversely, mediodorsal thalamus responses reflected the statistical regularity of cue presentation and were required for switching between such experimentally specified cueing contexts. A subset of these thalamic responses sustained context relevant PFC representations, while another suppressed the context irrelevant ones. Through modeling and experimental validation, we find that thalamic mediated suppression may not only reduce PFC representational interference but could also preserve unused cortical traces for future use. Overall, our study provides a computational foundation for thalamic engagement in cognitive flexibility.Rikhye et al. recorded prefrontal and thalamic populations from mice performing attention selection across different contexts. By encoding context, the thalamus both enhances and suppresses prefrontal representations in a context appropriate manner.
Nature Neuroscience