Enhancement of GABA release through endogenous activation of axonal GABA(A) receptors in juvenile cerebellum

J Neurosci. 2007 Nov 14;27(46):12452-63. doi: 10.1523/JNEUROSCI.3413-07.2007.


Recent evidence indicates the presence of presynaptic GABA(A) receptors (GABA(A)Rs) in the axon domain of several classes of central neurons, including cerebellar basket and stellate cells. Here, we investigate the possibility that these receptors could be activated in the absence of electrical or chemical stimulation. We find that low concentrations of GABA increase the frequency of miniature GABAergic synaptic currents. Submaximal concentrations of a GABA(A)R blocker, gabazine, decrease both the miniature current frequency and the probability of evoked GABA release. Zolpidem, an agonist of the benzodiazepine binding site, and NO-711 (1-[2-[[(diphenylmethylene)imino]oxy]ethyl]-1,2,5,6-tetrahydro-3-pyridinecarboxylic acid hydrochloride), a blocker of GABA uptake, both increase the frequency of miniature currents. These effects occur up to postnatal day 14, but not later. Immunohistochemistry indicates the presence of alpha1-containing GABA(A)Rs in interneuron presynaptic terminals with a similar age dependence. We conclude that, under resting conditions, axonal GABA(A)Rs are significantly activated, that this activation results in enhanced GABA release, and that it can be augmented by increasing the affinity of GABA(A)Rs or reducing GABA uptake. Our findings suggest the existence of a positive-feedback mechanism involving presynaptic GABA(A)Rs that maintains a high release rate and a high local GABA concentration in the immature cerebellar network.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Axons / drug effects
  • Axons / metabolism*
  • Cerebellum / cytology
  • Cerebellum / growth & development*
  • Cerebellum / metabolism*
  • GABA-A Receptor Agonists
  • GABA-A Receptor Antagonists
  • Inhibitory Postsynaptic Potentials / drug effects
  • Inhibitory Postsynaptic Potentials / physiology
  • Interneurons / metabolism
  • Neural Inhibition / drug effects
  • Neural Inhibition / physiology
  • Neural Pathways / cytology
  • Neural Pathways / growth & development
  • Neural Pathways / metabolism
  • Organ Culture Techniques
  • Presynaptic Terminals / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, GABA-A / drug effects
  • Receptors, GABA-A / metabolism*
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology*
  • gamma-Aminobutyric Acid / metabolism*
  • gamma-Aminobutyric Acid / pharmacology


  • GABA-A Receptor Agonists
  • GABA-A Receptor Antagonists
  • Receptors, GABA-A
  • gamma-Aminobutyric Acid