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Keywords:

  • entrainment;
  • GABAB receptors;
  • gamma;
  • hippocampus;
  • inhibitory postsynaptic potential;
  • rat

Abstract

In the mammalian central nervous system, GABAB receptors mediate slow pre- and postsynaptic inhibition. Using rat hippocampal slices we investigated the role of synaptic GABAB receptors in regulating kainate-induced subthreshold neuronal network oscillations in the gamma frequency range (25–80 Hz). The GABAB receptor agonist baclofen largely eliminated gamma oscillations. The GABAB receptor antagonist CGP55845 reversed this action of baclofen but alone did not alter the power or frequency of ongoing oscillations. To examine the role of synaptically released GABA on network activity, we electrically stimulated stratum radiatum of CA3 whilst recording gamma oscillations from stratum pyramidale. Single stimuli produced a pronounced transient (up to 1 s in duration) inhibition of gamma frequency oscillations. This stimulus-induced shutdown of network activity was enhanced by the GABA uptake inhibitor tiagabine and largely inhibited by CGP55845. Multiple stimuli delivered at frequencies of 1–3 Hz resulted in an activity-dependent fatigue of the inhibition of gamma activity, such that, after a number of stimuli, oscillations could be detected tens of milliseconds after the stimulus. Interestingly, this activity-dependent fatigue of inhibition uncovered a stimulus-dependent temporal entrainment of the gamma oscillations. Furthermore, the amount of repetitive synaptic input that was required to cause this entrainment was dramatically reduced by GABAB receptor antagonism such that it was evident within just a few stimuli. These data suggest that convergent afferent synaptic activity can alter the precise temporal arrangement of neuronal network activity. Furthermore, the flow of such information into a functioning neuronal network is highly regulated by GABAB receptor-mediated synaptic inhibition.