Nucleus basalis-enabled stimulus-specific plasticity in the visual cortex is mediated by astrocytes

Proc Natl Acad Sci U S A. 2012 Oct 9;109(41):E2832-41. doi: 10.1073/pnas.1206557109. Epub 2012 Sep 24.


Although cholinergic innervation of the cortex by the nucleus basalis (NB) is known to modulate cortical neuronal responses and instruct cortical plasticity, little is known about the underlying cellular mechanisms. Using cell-attached recordings in vivo, we demonstrate that electrical stimulation of the NB, paired with visual stimulation, can induce significant potentiation of visual responses in excitatory neurons of the primary visual cortex in mice. We further show with in vivo two-photon calcium imaging, ex vivo calcium imaging, and whole-cell recordings that this pairing-induced potentiation is mediated by direct cholinergic activation of primary visual cortex astrocytes via muscarinic AChRs. The potentiation is absent in conditional inositol 1,4,5 trisphosphate receptor type 2 KO mice, which lack astrocyte calcium activation, and is stimulus-specific, because pairing NB stimulation with a specific visual orientation reveals a highly selective potentiation of responses to the paired orientation compared with unpaired orientations. Collectively, these findings reveal a unique and surprising role for astrocytes in NB-induced stimulus-specific plasticity in the cerebral cortex.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / pharmacology
  • Animals
  • Astrocytes / cytology
  • Astrocytes / metabolism
  • Astrocytes / physiology*
  • Atropine / pharmacology
  • Basal Nucleus of Meynert / cytology
  • Basal Nucleus of Meynert / metabolism
  • Basal Nucleus of Meynert / physiology*
  • Calcium / metabolism
  • Cerebral Cortex / cytology
  • Cerebral Cortex / metabolism
  • Cerebral Cortex / physiology
  • Chelating Agents / pharmacology
  • Cholinergic Agonists / pharmacology
  • Egtazic Acid / analogs & derivatives
  • Egtazic Acid / pharmacology
  • Evoked Potentials / drug effects
  • Excitatory Postsynaptic Potentials / drug effects
  • Immunohistochemistry
  • In Vitro Techniques
  • Inositol 1,4,5-Trisphosphate Receptors / genetics
  • Inositol 1,4,5-Trisphosphate Receptors / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Muscarinic Antagonists / pharmacology
  • Neuronal Plasticity / drug effects
  • Neuronal Plasticity / physiology*
  • Patch-Clamp Techniques
  • Photic Stimulation
  • Receptors, Muscarinic / metabolism
  • Visual Cortex / cytology
  • Visual Cortex / metabolism
  • Visual Cortex / physiology*


  • Chelating Agents
  • Cholinergic Agonists
  • Inositol 1,4,5-Trisphosphate Receptors
  • Muscarinic Antagonists
  • Receptors, Muscarinic
  • Egtazic Acid
  • Atropine
  • 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid
  • Acetylcholine
  • Calcium