M1 muscarinic receptors boost synaptic potentials and calcium influx in dendritic spines by inhibiting postsynaptic SK channels

Neuron. 2010 Dec 9;68(5):936-47. doi: 10.1016/j.neuron.2010.09.004.


Acetylcholine release and activation of muscarinic cholinergic receptors (mAChRs) enhance synaptic plasticity in vitro and cognition and memory in vivo. Within the hippocampus, mAChRs promote NMDA-type glutamate receptor-dependent forms of long-term potentiation. Here, we use calcium (Ca) imaging combined with two-photon laser glutamate uncaging at apical spines of CA1 pyramidal neurons to examine postsynaptic mechanisms of muscarinic modulation of glutamatergic transmission. Uncaging-evoked excitatory postsynaptic potentials and Ca transients are increased by muscarinic stimulation; however, this is not due to direct modulation of glutamate receptors. Instead, mAChRs modulate a negative feedback loop in spines that normally suppresses synaptic signals. mAChR activation reduces the Ca sensitivity of small conductance Ca-activated potassium (SK) channels that are found in the spine, resulting in increased synaptic potentials and Ca transients. These effects are mediated by M1-type muscarinic receptors and occur in a casein kinase-2-dependent manner. Thus, muscarinic modulation regulates synaptic transmission by tuning the activity of nonglutamatergic postsynaptic ion channels.

Publication types

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

MeSH terms

  • Acetylcholine / metabolism
  • Animals
  • CA1 Region, Hippocampal / cytology
  • CA1 Region, Hippocampal / metabolism
  • Calcium / metabolism
  • Casein Kinase II / metabolism*
  • Dendritic Spines / metabolism*
  • Feedback, Physiological
  • In Vitro Techniques
  • Mice
  • Mice, Inbred C57BL
  • Pyramidal Cells / cytology
  • Pyramidal Cells / metabolism
  • Receptor Cross-Talk / physiology*
  • Receptor, Muscarinic M1 / metabolism*
  • Second Messenger Systems / physiology
  • Signal Transduction / physiology
  • Small-Conductance Calcium-Activated Potassium Channels / metabolism*
  • Synaptic Potentials / physiology


  • Receptor, Muscarinic M1
  • Small-Conductance Calcium-Activated Potassium Channels
  • Casein Kinase II
  • Acetylcholine
  • Calcium