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

Naiyan Chen1, Hiroki Sugihara, Jitendra Sharma

  • 1Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

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Cholinergic nucleus basalis (NB) stimulation potentiates visual cortex responses by activating astrocytes. This astrocyte activation drives stimulus-specific plasticity, revealing a novel cellular mechanism for cortical learning.

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Area of Science:

  • Neuroscience
  • Cellular Biology
  • Systems Neuroscience

Background:

  • Cholinergic input from the nucleus basalis (NB) modulates cortical activity and plasticity.
  • The precise cellular mechanisms underlying NB-induced cortical plasticity remain largely unknown.
  • Astrocytes, once considered passive support cells, are increasingly recognized for their active role in neuronal function.

Purpose of the Study:

  • To elucidate the cellular mechanisms by which nucleus basalis (NB) stimulation induces plasticity in the primary visual cortex.
  • To investigate the role of astrocytes in mediating cholinergic-induced potentiation of visual responses.
  • To determine if NB-induced plasticity is stimulus-specific.

Main Methods:

  • In vivo cell-attached recordings to assess neuronal responses.
  • In vivo two-photon calcium imaging and ex vivo calcium imaging to monitor astrocyte activity.
  • Whole-cell recordings and conditional knockout mouse models (inositol 1,4,5 trisphosphate receptor type 2) to assess calcium signaling pathways.

Main Results:

  • Pairing NB stimulation with visual stimuli potentiated visual responses in primary visual cortex excitatory neurons.
  • This potentiation was mediated by direct cholinergic activation of astrocytes via muscarinic acetylcholine receptors (AChRs).
  • The potentiation was absent in mice lacking astrocyte calcium activation and was highly stimulus-specific, favoring the paired visual orientation.

Conclusions:

  • Astrocytes play a crucial role in NB-induced stimulus-specific plasticity in the cerebral cortex.
  • Cholinergic activation of astrocytes is a key cellular mechanism underlying cortical learning and adaptation.
  • These findings reveal a novel pathway for modulating cortical sensory processing and plasticity.