The brain processes sensory decisions by activating primary sensory cortex followed by higher order cortical areas. Yet data in the last few years has shown that it is not the direct corticocortical projections that are important but rather the cortico-thalamo-cortical pathways, challenging the cortex-centric view of perception. We have found that these transthalamic pathways between sensory cortices propagate reward-relevant information for perceptual decisions. However, it is unknown if these pathways also link other brain regions to support decision-making in frontal cortex.

We used rabies trans-synaptic tracing to establish the first evidence of a transthalamic pathway linking secondary sensory cortex to frontal cortex, providing an alternative feedforward route for frontal cortex activation during perception.

To understand the function of transthalamic pathways during decision processing, we trained water-restricted mice on a head-fixed whisker perceptual task and recorded GCaMP6m-expressing neuronal activity using a ‘miniscope’ attached to a lens in higher order thalamus. Optogenetic tagging of corticothalamic inputs allowed identification of thalamic cells that receive input from the transthalamic pathway.

Importantly, between the sensory stimulation and choice epochs of the task, there was a ‘delay’ period during which preparatory choice activity is maintained. Surprisingly, on correct trials, 17% of higher order thalamic cells showed persistent activity across the delay period suggesting that higher order processing in frontal cortex could be driven by higher order thalamus.

Transthalamic pathways thus support the maintenance of choice or preparatory information for correct sensory decisions and challenge the textbook ‘map’ of decision-making, which should include signalling via the thalamus.