The vertical architecture of the neocortex, encapsulated in the concept of the cortical column, remains central to our grasp of cortical function. Paradoxically, the outermost layers remain enigmatic - layer 1 at the top and layer 6b (that Cajal termed layer 7) at the bottom - are still shrouded in mystery. Emerging evidence underscores their critical roles in sculpting the thalamo-cortical loop, crucial for conscious perception. In collaboration with the Kubota group, we've highlighted layer 1's significance in long-term memory storage, showing its pivotal role in overseeing spine dynamics during motor learning and the resulting behavioral adaptations.

In this talk, I will present new data unveiling the intricacies of these outer layers. Layer 6b, with its distinctive links to the orexinergic system, emerges as a key modulator of cortical states and an orchestrator of the dialogue between the cortex and higher-order thalamus.  Using optogenetics and and novel circuit-mapping techniques, we show that although layer 6b receives exclusively cortico-cortical input, the output of L6b targets the same cortical layers as higher-order thalamus, serving as a second thalamus and bolstering active cortical states. By exerting control, especially over layer 1, it emerges as a strategic hub for both top-down and bottom-up communication, modulating the intrinsic attributes of pyramidal neuron tuft dendrites. This modulation, in turn, refines the overall cortical column output and the feedback directed to the higher-order thalamus. Our findings shed light on the nuanced interactions between local and long-range inputs, painting a richer picture of their collective influence on cortical output.