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

Qi, G., Yang, D., Messore, L. F., Bast, A., Yáñez, F., Oberlaender, M., et al. (2025). FOXP2-immunoreactive corticothalamic neurons in neocortical layers 6a and 6b are tightly regulated by neuromodulatory systems. iScience, 28(1): 111646. doi:10.1016/j.isci.2024.111646.

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 Creators:
Qi, Guanxiao1, Author
Yang, Danqing1, Author
Messore, Luis Fernando2, Author                 
Bast, Arco2, Author                 
Yáñez, Felipe2, Author                 
Oberlaender, Marcel2, Author                 
Feldmeyer, Dirk1, Author
Affiliations:
1External Organizations, ou_persistent22              
2Max Planck Research Group In Silico Brain Sciences, Max Planck Institute for Neurobiology of Behavior – caesar, Max Planck Society, ou_3361774              

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Free keywords: HIGHLIGHTS • All L6 FOXP2+ pyramids innervate thalamus; L6b FOXP2+ cells target only higher-order nuclei • L6a and L6b FOXP2+ cells form facilitating synapses, enabling profound signal amplification • Strong cholinergic response in L6a and L6b FOXP2+ CT cells via α4β2α5 nicotinic receptors • Robust dopamine D1 response in L6b FOXP2+ cells, indicating a unique modulatory mechanism
 Abstract: The FOXP2/Foxp2 gene, linked to fine motor control in vertebrates, is a potential candidate gene thought to play a prominent role in human language production. It is expressed specifically in a subset of corticothalamic (CT) pyramidal cells (PCs) in layer 6 (L6) of the neocortex. These L6 FOXP2+ PCs project exclusively to the thalamus, with L6a PCs targeting first-order or both first- and higher-order thalamic nuclei, whereas L6b PCs connect only to higher-order nuclei. Synaptic connections established by both L6a and L6b FOXP2+ PCs have low release probabilities and respond strongly to acetylcholine (ACh), triggering action potential (AP) trains. Notably, L6b FOXP2− PCs are more sensitive to ACh than L6a, and L6b FOXP2+ PCs also react robustly to dopamine. Thus, FOXP2 labels L6a and L6b CT PCs, which are precisely regulated by neuromodulators, highlighting their roles as potent modulators of thalamic activity.

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Language(s): eng - English
 Dates: 2024-12-172025-01-17
 Publication Status: Issued
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 Rev. Type: Peer
 Identifiers: DOI: 10.1016/j.isci.2024.111646
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Title: iScience
Source Genre: Journal
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Publ. Info: Amsterdam ; Bosten ; London ; New York ; Oxford ; Paris ; Philadelphia ; San Diego ; St. Louis : Elsevier
Pages: - Volume / Issue: 28 (1) Sequence Number: 111646 Start / End Page: - Identifier: ISSN: 2589-0042
CoNE: https://pure.mpg.de/cone/journals/resource/2589-0042