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bioRxiv · 10.1101/2024.06.21.599838

FOXP2-immunoreactive, corticothalamic pyramidal cells in neocortical layers 6a and 6b are tightly regulated by neuromodulatory systems

Qi, G.·Yang, D.·Messore, F.·Bast, A.·Yanez, F.·Oberlaender, M.·Feldmeyer, D.
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Abstract

The FOXP2/Foxp2 gene is involved in fine motor control in many vertebrate species; in humans, it is one of the candidate genes thought to play a prominent role in language production. Several studies suggest that in the neocortex, Foxp2 is exclusively expressed in a subset of corticothalamic (CT) pyramidal cells (PCs) in layer 6 (L6). However, the morphological and intrinsic electrophysiological, synaptic and neuromodulatory properties of Foxp2-expressing L6 PCs remain largely unknown. Here we systematically characterise these properties for FOXP2-positive (FOXP2+) PCs across L6 in the rat somatosensory cortex. We find that L6 FOXP2+ PCs are distinct in all of these properties from those of L6 FOXP2-negative (FOXP2-) neuronal cell types. We show that L6 FOXP2+ PCs project exclusively to thalamus. In upper L6 (L6a), FOXP2+ PCs innervate either the first-order thalamus or both first and higher-order thalamic nuclei. FOXP2+ PCs in deep L6 (L6b) project almost exclusively to higher-order thalamus. Synaptic connections established by L6a and L6b FOXP2+ PCs exhibit low synaptic release probability, whereas L6 corticocortical PCs have a high release probability. Both L6a and L6b FOXP2+ PCs respond strongly to acetylcholine (ACh), which in the absence of TTX results in firing of action potential (AP) trains. Notably, L6b but not L6a FOXP2- PCs are highly sensitive to ACh. In addition, L6b FOXP2+ PCs close to the white matter border show strong responses to dopamine that develop into prolonged AP firing. Our data suggest that FOXP2 is a marker for CT PCs in L6 that are strongly controlled by neurotransmitters such as ACh and dopamine. These findings are in line with a pivotal role for both L6a and L6b CT PCs as modulators of thalamic activity.

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Qi, G., Yang, D., Messore, F., Bast, A., Yanez, F., Oberlaender, M., Feldmeyer, D.. 2024-06-22. FOXP2-immunoreactive, corticothalamic pyramidal cells in neocortical layers 6a and 6b are tightly regulated by neuromodulatory systems. https://doi.org/10.1101/2024.06.21.599838

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