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Cell-type-specific modulation of neocortical activity by basal forebrain input.

Henry J Alitto1, Yang Dan

  • 1Division of Neurobiology, Department of Molecular and Cell Biology, Helen Wills Neuroscience Institute, Howard Hughes Medical Institute, University of California Berkeley, CA, USA.

Frontiers in Systems Neuroscience
|January 15, 2013
PubMed
Summary

Cholinergic neurons in the basal forebrain modulate cortical neuron activity. Different neuron types respond uniquely to acetylcholine (ACh) via muscarinic and nicotinic receptors during arousal and attention.

Keywords:
acetylcholinelayer 1parvalbuminvasoactive intestinal peptidevisual cortex

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Area of Science:

  • Neuroscience
  • Cellular Neuroscience
  • Systems Neuroscience

Background:

  • Cholinergic neurons in the basal forebrain (BF) are crucial for arousal and attention.
  • BF cholinergic activation desynchronizes cortical activity and enhances sensory processing.
  • The precise modulation of distinct cortical neuron subtypes by cholinergic input remains poorly understood.

Purpose of the Study:

  • To investigate how basal forebrain (BF) cholinergic input differentially modulates the activity of excitatory and inhibitory neuron subtypes in the mouse visual cortex.
  • To elucidate the roles of muscarinic and nicotinic acetylcholine receptors (mAChRs and nAChRs) in mediating these effects.
  • To understand how these modulations change with varying levels of cortical desynchronization.

Main Methods:

  • In vivo two-photon calcium imaging was employed to monitor neuronal activity in layers 1 and 2/3 of the mouse visual cortex.
  • Electrical stimulation of the basal forebrain (BF) was used to activate cholinergic pathways.
  • Pharmacological manipulation targeting muscarinic and nicotinic acetylcholine receptors (mAChRs and nAChRs) was performed.

Main Results:

  • BF stimulation induced bidirectional modulation of both excitatory neurons and several inhibitory interneuron subtypes.
  • Glutamatergic activity contributed to activating both excitatory and inhibitory neurons.
  • Acetylcholine (ACh) exhibited complex effects: excitatory and parvalbumin-positive (PV+) neurons were activated via mAChRs at low cortical desynchronization and suppressed via nAChRs at high desynchronization.
  • Vasoactive intestinal peptide-positive (VIP+) and layer 1 interneurons were preferentially activated via nAChRs during strong cortical desynchronization.

Conclusions:

  • Cholinergic input from the BF significantly shifts the relative activity of distinct cortical neuron subtypes.
  • These shifts are dependent on the level of cortical desynchronization.
  • The differential roles of mAChRs and nAChRs highlight a complex regulatory mechanism of cortical processing by the BF cholinergic system.