Cholinergic modulation amplifies the intrinsic oscillatory properties of CA1 hippocampal cholecystokinin-positive interneurons

J Physiol. 2011 Feb 1;589(Pt 3):609-27. doi: 10.1113/jphysiol.2010.199422. Epub 2010 Nov 29.


In the mammalian hippocampus, the neurotransmitter acetylcholine (ACh) promotes learning and memory storage. During sensory processing and learning, large ACh-dependent electrical oscillatory events are observed, which involve the synchronization of both inhibitory and excitatory neural circuits. While the actions of ACh are known on excitatory hippocampal circuits, its actions on specific inhibitory circuits are poorly understood. We show that two types of cholecystokinin-positive local circuit inhibitory interneuron, the so-called 'basket cells' and 'Schaffer collateral-associated' cells, which innervate separately the cell body and dendritic regions of principal cells, are modulated similarly by cholinergic receptor activation. In both cell types activation of their muscarinic receptors triggers a general increase of excitability and intrinsic oscillatory activity, and a more efficient engagement to slow network oscillations. Knowledge of how cholinergic neuromodulation acts on neurochemically identical but morphologically distinct inhibitory interneurons will allow us to understand the role played by this important neuromodulator during hippocampal-dependent tasks in vivo.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology*
  • Animals
  • CA1 Region, Hippocampal / cytology
  • CA1 Region, Hippocampal / physiology*
  • Cholecystokinin / genetics
  • Cholecystokinin / metabolism*
  • Cholinergic Fibers / physiology*
  • Electrophysiological Phenomena / drug effects
  • Electrophysiological Phenomena / physiology
  • Gene Expression / genetics
  • Glutamate Decarboxylase / genetics
  • Green Fluorescent Proteins / genetics
  • Interneurons / cytology
  • Interneurons / drug effects
  • Interneurons / physiology*
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Muscarine / pharmacology
  • Receptor, Muscarinic M1 / genetics
  • Receptor, Muscarinic M1 / metabolism
  • Receptor, Muscarinic M3 / genetics
  • Receptor, Muscarinic M3 / metabolism


  • Receptor, Muscarinic M1
  • Receptor, Muscarinic M3
  • Green Fluorescent Proteins
  • Muscarine
  • Cholecystokinin
  • Glutamate Decarboxylase
  • glutamate decarboxylase 2