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Layer 6 is a hub for cholinergic modulation in the mouse auditory cortex.

Lucas G Vattino1,2, Kameron K Clayton1,2, Troy A Hackett3

  • 1Eaton-Peabody Laboratories, Massachusetts Eye and Ear, 243 Charles St, Boston, MA 02114, United States.

Cerebral Cortex (New York, N.Y. : 1991)
|January 22, 2026
PubMed
Summary
This summary is machine-generated.

Basal forebrain cholinergic neurons (BFCNs) modulate the auditory cortex via distinct pathways. They activate layer 6 pyramidal neurons (L6-PNs) and layer 1 inhibitory neurons (L1-INs) through different receptors, impacting brain states and perception.

Keywords:
acetylcholinebasal forebrainlayer 6 corticothalamic neuronsneuromodulationnicotinic and muscarinic receptors

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Area of Science:

  • Neuroscience
  • Cellular Neuroscience
  • Systems Neuroscience

Background:

  • Basal forebrain cholinergic neurons (BFCNs) extensively innervate the auditory cortex (ACtx).
  • Acetylcholine (ACh) rapidly modulates cortical circuits via nicotinic receptors (nAChRs) on layer 1 inhibitory neurons (L1-INs).
  • The role of BFCNs in deeper cortical layers remains less understood.

Purpose of the Study:

  • To investigate the functional impact of BFCNs on deeper cortical layers, specifically layer 6 pyramidal neurons (L6-PNs).
  • To identify the specific acetylcholine receptors involved in BFCN modulation of L6-PNs.
  • To elucidate the parallel pathways BFCNs utilize for cortical circuit modulation.

Main Methods:

  • Multi-plex in situ labeling to analyze receptor expression across cortical layers and cell types.
  • In vivo optogenetic activation of BFCN axons to study neuronal responses in different cortical layers.
  • Acute slice electrophysiology to record postsynaptic potentials in L6-PNs following BFCN activation.

Main Results:

  • Layer 6 pyramidal neurons (L6-PNs) express diverse nicotinic (nAChR) and muscarinic (mAChR) acetylcholine receptor subunits.
  • Optogenetic BFCN activation caused persistent modulation in layers 2-6 but rapid phasic activation specifically in L6.
  • BFCN activation elicited fast nAChR-mediated excitation and slower mAChR-mediated inhibition in L6-PNs.

Conclusions:

  • BFCNs modulate cortical circuits through distinct pathways involving L1-INs and excitatory L6-PNs.
  • Cholinergic control involves parallel pathways, coupling fast, transient modulation with slower, sustained regulation.
  • These parallel pathways shape cortical perception and plasticity through differential receptor and circuit engagement.