Differential GABAB-receptor-mediated effects in perisomatic- and dendrite-targeting parvalbumin interneurons Journal Article

Author(s): Booker, Sam A; Gross, Anna; Althof, Daniel; Shigemoto, Ryuichi; Bettler, Bernhard; Frotscher, Michael; Hearing, Matthew C; Wickman, Kevin D; Watanabe, Masahiko; Kulik, Ákos; Vida, Imre
Article 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 gammafrequency oscillations in cortical networks. Fast GABAergic input onto PVIs is crucial for their synchronization and oscillatory entrainment, but the role of metabotropic GABAB receptors (GABABRs) 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 GABABRs 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 forGABABRs 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 GABABR-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 GABABR 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 GABAB IPSCs can phasically modulate the discharge of PT interneurons at theta frequencies. In summary, our results show that GABABRs 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 GABABRs may shift the balance between perisomatic and dendritic inhibition.
Keywords: Cholecystokinin; 4 aminobutyric acid B receptor; parvalbumin; 4 aminobutyric acid; G protein coupled inwardly rectifying potassium channel; GABAergic receptor affecting agent; green fluorescent protein; neuropeptide Y; nipecotic acid derivative; tiagabine; vesicular inhibitory amino acid transporter; Viaat protein, rat
Journal Title: Journal of Neuroscience
Volume: 33
Issue 18
ISSN: 1529-2401
Publisher: Society for Neuroscience  
Date Published: 2013-05-01
Start Page: 7961
End Page: 7974
DOI: 10.1523/JNEUROSCI.1186-12.2013
Open access: no