GABAB receptors inhibit dendrodendritic transmission in the rat olfactory bulb

Abstract

In the mammalian olfactory bulb, mitral cell dendrites release glutamate onto the dendritic spines of granule cells, which in turn release GABA back onto mitral dendrites. This local synaptic circuit forms the basis for reciprocal dendrodendritic inhibition mediated by ionotropic GABAA receptors in mitral cells. Surprisingly little is known about neurotransmitter modulation of dendrodendritic signaling in the olfactory bulb. In this study, we examine whether metabotropic GABAB receptors modulate dendrodendritic signaling between mitral and granule cells. We find that the selective GABAB agonist baclofen reduces mitral cell recurrent inhibition mediated by dendrodendritic synapses. GABAB receptor activation causes only a weak inhibition of field EPSCs in the external plexiform layer and only slightly reduces glutamate-mediated mitral cell self-excitation. Although GABAB receptors depress mitral cell glutamate release only weakly, baclofen causes a marked reduction in the amplitude of granule-cell-evoked, GABAA-mediated IPSCs in mitral cells. In addition to reducing the amplitude of granule-cell-evoked IPSCs, baclofen causes a change from paired-pulse depression to paired-pulse facilitation, suggesting that GABAB receptors modulate GABA release from granule cells. To explore the mechanism of action of GABAB receptors further, we show that baclofen inhibits high-voltage-activated calcium currents in granule cells. Together, these findings suggest that GABAB receptors modulate dendrodendritic inhibition primarily by inhibiting granule cell calcium channels and reducing the release of GABA. Furthermore, we show that endogenous GABA regulates the strength of dendrodendritic inhibition via the activation of GABAB autoreceptors.