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Although interactions between the thalamus and cortex are critical for cognitive function1-3, the exact contribution of the thalamus to these interactions remains unclear. Recent studies have shown diverse connectivity patterns across the thalamus4,5, but whether this diversity translates to thalamic functions beyond relaying information to or between cortical regions6 is unknown. Here we show, by investigating the representation of two rules used to guide attention in the mouse prefrontal cortex (PFC), that the mediodorsal thalamus sustains these representations without relaying categorical information. Specifically, mediodorsal input amplifies local PFC connectivity, enabling rule-specific neural sequences to emerge and thereby maintain rule representations. Consistent with this notion, broadly enhancing PFC excitability diminishes rule specificity and behavioural performance, whereas enhancing mediodorsal excitability improves both. Overall, our results define a previously unknown principle in neuroscience; thalamic control of functional cortical connectivity. This function, which is dissociable from categorical information relay, indicates that the thalamus has a much broader role in cognition than previously thought.

(ProQuest: ... denotes formulae omitted.)

We recorded PFC ensembles in a two-alternative forced choice (2AFC) task, in which a freely behaving mouse selected between conflicting visual and auditory stimuli based on whether one of two rules was presented, and where rule presentation was varied on a trial- by-trial basis (Fig. 1a). Broadband white noise was informative of trial availability, prompting trial initiation by snout-protrusion into a centrally located port. Subsequently, either low-pass (10 kHz) or high-pass (11 kHz) noise was presented for 100 ms to signal the task rules (rule 1 (low pass), attend to vision; rule 2 (high pass), attend to audition), and after a brief delay where the head position was stably maintained, the animal selected between spatially conflicting visual and auditory stimuli to receive a reward. Animals achieved a balanced and robust performance across modalities (Extended Data Fig. 1a) and no stereotypical behaviour, which indicates a modality or location preference, was observed during the delay. These findings suggest that animals were capable of holding the task rule 'in mind' and using it to map onto sensory targets.

Given that prelimbic cortex7 activity during the delay (referred to as prefrontal cortex (PFC)) is necessary for task performance8, we directly interrogated its neural substrates (Extended Data Fig. 1b-d). We found that certain PFC neurons signalled...

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