Presynaptic inhibition of Schaffer collateral synapses by stimulation of hippocampal cholinergic afferent fibres

Eur J Neurosci. 2003 Feb;17(3):555-8. doi: 10.1046/j.1460-9568.2003.02490.x.


It has been known for decades that muscarinic agonists presynaptically inhibit Schaffer collateral synapses contacting hippocampal CA1 pyramidal neurons. However, a demonstration of the inhibition of Schaffer collateral synapses induced by acetylcholine released by cholinergic hippocampal afferents is lacking. We present original results showing that electrical stimulation at the stratum oriens/alveus with brief stimulus trains inhibited excitatory postsynaptic currents evoked by stimulation of Schaffer collaterals in CA1 pyramidal neurons of rat hippocampal slices. The increased paired-pulse facilitation and the changes in the variance of excitatory postsynaptic current amplitude that paralleled the inhibition suggest that it was mediated presynaptically. The effects of oriens/alveus stimulation were inhibited by atropine, and blocking nicotinic receptors with methyllycaconitine was ineffective, suggesting that the inhibition was mediated via the activation of presynaptic muscarinic receptors. The results provide a novel demonstration of the presynaptic inhibition of glutamatergic neurotransmission by cholinergic fibres in the hippocampus, implying that afferent cholinergic fibres regulate the strength of excitatory synaptic transmission.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Atropine / pharmacology
  • Cholinergic Fibers / metabolism
  • Cholinergic Fibers / physiology*
  • Electric Stimulation
  • Excitatory Postsynaptic Potentials / physiology
  • Glutamic Acid / metabolism
  • Hippocampus / cytology
  • Hippocampus / metabolism
  • Hippocampus / physiology*
  • Membrane Potentials / physiology
  • Muscarinic Antagonists / pharmacology
  • Neurons, Afferent / metabolism
  • Neurons, Afferent / physiology
  • Patch-Clamp Techniques
  • Rats
  • Rats, Wistar
  • Receptors, Presynaptic / metabolism
  • Receptors, Presynaptic / physiology*
  • Synapses / metabolism
  • Synapses / physiology*


  • Muscarinic Antagonists
  • Receptors, Presynaptic
  • Glutamic Acid
  • Atropine