Role of glutamate autoreceptors at hippocampal mossy fiber synapses

Neuron. 2008 Dec 26;60(6):1082-94. doi: 10.1016/j.neuron.2008.10.045.


Presynaptic autoreceptors modulate transmitter release at many synapses. At the mossy fiber to CA3 pyramidal cell (mf-CA3) synapse, two types of glutamatergic autoreceptors have been identified: transmitter release is reportedly suppressed by metabotropic glutamate receptors (mGluRs) and augmented by kainate receptors (KARs). However, the net effect of these autoreceptors when activated by endogenous glutamate is unknown. Here, we show that during low-frequency mossy fiber stimulation, glutamate acting through presynaptic mGluRs substantially suppresses transmitter release. However, using similar recording conditions, we find that presynaptic KARs are insufficient to facilitate transmitter release over a wide range of mossy fiber stimulus frequencies, indicating that the uniquely robust mf-CA3 short-term plasticity is KAR independent. Furthermore, we report that actions generally attributed to presynaptic KARs are likely due to activation of recurrent CA3 network activity. Thus, negative feedback via presynaptic mGluRs is the dominant mode of glutamatergic autoregulation at the mf-CA3 synapse.

Publication types

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

MeSH terms

  • Animals
  • Animals, Newborn
  • Autoreceptors / physiology*
  • Biophysics
  • Calcium / pharmacology
  • Cyclopropanes / pharmacology
  • Electric Stimulation / methods
  • Excitatory Amino Acid Agonists / pharmacology
  • Excitatory Amino Acid Antagonists / pharmacology
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / genetics
  • Excitatory Postsynaptic Potentials / physiology
  • Glycine / analogs & derivatives
  • Glycine / pharmacology
  • Hippocampus / cytology*
  • In Vitro Techniques
  • Kainic Acid / pharmacology
  • Mice
  • Mice, Knockout
  • Mossy Fibers, Hippocampal / physiology*
  • Neurons / physiology*
  • Patch-Clamp Techniques / methods
  • Presynaptic Terminals / physiology
  • Rats
  • Receptors, Glutamate / deficiency
  • Receptors, Glutamate / physiology*
  • Sodium Channel Blockers / pharmacology
  • Synapses / drug effects
  • Synapses / physiology*
  • Tetrodotoxin / pharmacology


  • Autoreceptors
  • Cyclopropanes
  • Excitatory Amino Acid Agonists
  • Excitatory Amino Acid Antagonists
  • Receptors, Glutamate
  • Sodium Channel Blockers
  • 2-(2,3-dicarboxycyclopropyl)glycine
  • Tetrodotoxin
  • Kainic Acid
  • Calcium
  • Glycine