Differential GABAB-Receptor-Mediated Effects in Perisomatic- and Dendrite-Targeting Parvalbumin Interneurons

摘要: Inhibitory parvalbumin-containing interneurons (PVIs) control neuronal discharge and support the generation of theta- gamma-frequency oscillations in cortical networks. Fast GABAergic input onto PVIs is crucial for their synchronization oscillatory entrainment, but role metabotropic GABAB receptors (GABABRs) mediating slow presynaptic postsynaptic inhibition remains unknown. In this study, we have combined high-resolution immunoelectron microscopy, whole-cell patch-clamp recording, computational modeling to investigate subcellular distribution effects GABABRs effector Kir3 channels rat hippocampal PVIs. Pre-embedding immunogold labeling revealed that localize at high levels extrasynaptic membrane parvalbumin-immunoreactive dendrites. Immunoreactivity was also present lower on PVI axon terminals. Whole-cell recordings further showed synaptically released GABA response extracellular stimulation evokes large GABABR-mediated IPSCs perisomatic-targeting (PT) PVIs, only small or no currents dendrite-targeting (DT) contrast, paired demonstrated GABABR activation results output synapses both PT DT more strongly latter. Finally, analysis indicated can phasically modulate theta frequencies. summary, our show differentially mediate contribute dynamic modulation activity during oscillations. Furthermore, these data provide evidence a compartment-specific molecular divergence subtypes, suggesting may shift balance between perisomatic dendritic inhibition.