title: Differential GABAB-receptor-mediated effects in perisomatic- and dendrite-targeting parvalbumin interneurons.
abstract: Inhibitory parvalbumin-containing interneurons (PVIs) control neuronal discharge and support the generation of theta- and gamma-frequency oscillations in cortical networks. Fast GABAergic input onto PVIs is crucial for their synchronization and oscillatory entrainment, but the role of metabotropic GABA(B) receptors (GABA(B)Rs) in mediating slow presynaptic and postsynaptic inhibition remains unknown. In this study, we have combined high-resolution immunoelectron microscopy, whole-cell patch-clamp recording, and computational modeling to investigate the subcellular distribution and effects of GABA(B)Rs and their postsynaptic effector Kir3 channels in rat hippocampal PVIs. Pre-embedding immunogold labeling revealed that the receptors and channels localize at high levels to the extrasynaptic membrane of parvalbumin-immunoreactive dendrites. Immunoreactivity for GABA(B)Rs was also present at lower levels on PVI axon terminals. Whole-cell recordings further showed that synaptically released GABA in response to extracellular stimulation evokes large GABA(B)R-mediated slow IPSCs in perisomatic-targeting (PT) PVIs, but only small or no currents in dendrite-targeting (DT) PVIs. In contrast, paired recordings demonstrated that GABA(B)R activation results in presynaptic inhibition at the output synapses of both PT and DT PVIs, but more strongly in the latter. Finally, computational analysis indicated that GABA(B) IPSCs can phasically modulate the discharge of PT interneurons at theta frequencies. In summary, our results show that GABA(B)Rs differentially mediate slow presynaptic and postsynaptic inhibition in PVIs and can contribute to the dynamic modulation of their activity during oscillations. Furthermore, these data provide evidence for a compartment-specific molecular divergence of hippocampal PVI subtypes, suggesting that activation of GABA(B)Rs may shift the balance between perisomatic and dendritic inhibition.
authors: NeuroCure Cluster of Excellence, Institute of Integrative Neuroanatomy, Charité, D-10117 Berlin, Germany.
authors: Sam A
authors: SA
authors: Booker
authors: Anna
authors: A
authors: Gross
authors: Daniel
authors: D
authors: Althof
authors: Ryuichi
authors: R
authors: Shigemoto
authors: Bernhard
authors: B
authors: Bettler
authors: Michael
authors: M
authors: Frotscher
authors: Matthew
authors: M
authors: Hearing
authors: Kevin
authors: K
authors: Wickman
authors: Masahiko
authors: M
authors: Watanabe
authors: Ákos
authors: Á
authors: Kulik
authors: Imre
authors: I
authors: Vida
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000378:metabolism / Q000648:ultrastructure; D002766:Cholecystokinin / Q000378:metabolism; D003198:Computer Simulation; D003712:Dendrites / Q000378:metabolism*; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000378:metabolism; D018682:GABA Agents / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000235:genetics; D006624:Hippocampus / Q000166:cytology*; D066298:In Vitro Techniques; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects / Q000235:genetics; D007395:Interneurons / Q000378:metabolism* / Q000648:ultrastructure*; D008297:Male; D008959:Models, Neurological; D009433:Neural Inhibition; D009478:Neuropeptide Y / Q000378:metabolism; D009557:Nipecotic Acids / Q000494:pharmacology; D010320:Parvalbumins / Q000378:metabolism*; D051381:Rats; D055647:Rats, Transgenic; D017208:Rats, Wistar; D018080:Receptors, GABA-B / Q000378:metabolism*; D000078308:Tiagabine; D050495:Vesicular Inhibitory Amino Acid Transport Proteins / Q000235:genetics / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D018682:GABA Agents; D009478:Neuropeptide Y; D009557:Nipecotic Acids; D010320:Parvalbumins; D018080:Receptors, GABA-B; C118623:Slc32a1 protein, rat; D050495:Vesicular Inhibitory Amino Acid Transport Proteins; D049452:Green Fluorescent Proteins; D005680:gamma-Aminobutyric Acid; D002766:Cholecystokinin; D000078308:Tiagabine
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