Region-selective control of the thalamic reticular nucleus via cortical layer 5 pyramidal cells

Corticothalamic pathways, responsible for the top-down control of the thalamus, have a canonical organization such that every cortical region sends output from both layer 6 (L6) and layer 5 (L5) to the thalamus. Here we demonstrate a qualitative, region-specific difference in the organization of mouse corticothalamic pathways. Specifically, L5 pyramidal cells of the frontal cortex, but not other cortical regions, establish monosynaptic connections with the inhibitory thalamic reticular nucleus (TRN). The frontal L5-TRN pathway parallels the L6-TRN projection but has distinct morphological and physiological features. The exact spike output of the L5-contacted TRN cells correlated with the level of cortical synchrony. Optogenetic perturbation of the L5-TRN connection disrupted the tight link between cortical and TRN activity. L5-driven TRN cells innervated thalamic nuclei involved in the control of frontal cortex activity. Our data show that frontal cortex functions require a highly specialized cortical control over intrathalamic inhibitory processes.

Automated summary

This study reveals the regional differences in the organization of corticothalamic pathways in mice, with a specific monosynaptic connection between L5 pyramidal cells in the frontal cortex and the inhibitory thalamic reticular nucleus (TRN). The control of TRN by the frontal cortex is different from other cortical regions and plays an important role in the control of frontal cortex activity.