ArticleCerebral cortex (New York, N.Y. : 1991)2026
Layer 6 is a hub for cholinergic modulation in the mouse auditory cortex.
Article in Cerebral cortex (New York, N.Y. : 1991), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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4 citing papers in PubMed.
- Noise-invariant representations of sound emerge along the canonical cortical hierarchy.PLoS biology · 2026Article
- Spontaneous and stimulus-driven arousal produce distinct acetylcholine dynamics across sensory and prefrontal cortex.bioRxiv : the preprint server for biology · 2026Article
- Layer 6 corticothalamic neurons show diverse and dynamic responses that support a role in cortical gain control in noisy environments.bioRxiv : the preprint server for biology · 2026Article
- Layer 5 and 6b extratelencephalic neurons encode distinct sound features in auditory cortex.bioRxiv : the preprint server for biology · 2026Article
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Abstract
Basal forebrain cholinergic neurons (BFCNs) densely innervate auditory cortex (ACtx), conveying signals linked to internal brain states and external sensory cues. Acetylcholine (ACh) is known to rapidly modulate cortical circuits through nicotinic ACh receptor (nAChR)-mediated activation of layer 1 inhibitory neurons (L1-INs). However, BFCN terminals are also abundant in deeper layers, where their functional impact has received less attention. Using multi-plex in situ labeling across cortical layers and cell types, we found that layer 6 pyramidal neurons (L6-PNs) are highly enriched in diverse transcripts for nAChR subunits and muscarinic ACh receptors (mAChRs). In vivo optogenetic activation of BFCN axons revealed persistent modulation of regular spiking units in L2-6 but a rapid phasic activation only in L6. In acute slices, optogenetic activation of BFCN axons elicited fast nAChR-mediated excitatory post-synaptic potentials in L6-PNs, comparable to responses in L1-INs, and slower mAChR-mediated inhibitory responses. These findings identify L1-INs and excitatory L6-PNs as two major hubs for BFCN modulation of cortical circuits. By recruiting distinct receptor mechanisms and circuit motifs in L1 and L6, BFCNs may engage parallel pathways of cholinergic control that couple fast, transient modulation with slower, sustained regulation to shape cortical perception and plasticity.
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