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

Booker, S.A. et al. (2013) Differential GABAB-receptor-mediated effects in perisomatic- and dendrite-targeting parvalbumin interneurons. Journal of Neuroscience, 33(18), pp. 7961-7974. (doi: 10.1523/JNEUROSCI.1186-12.2013)

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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<sub>B</sub> receptors (GABA<sub>B</sub>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<sub>B</sub>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<sub>B</sub>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<sub>B</sub>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<sub>B</sub>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<sub>B</sub> IPSCs can phasically modulate the discharge of PT interneurons at theta frequencies. In summary, our results show that GABA<sub>B</sub>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<sub>B</sub>Rs may shift the balance between perisomatic and dendritic inhibition.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Vida, Dr Imre
Authors: Booker, S.A., Gross, A., Althof, D., Shigemoto, R., Bettler, B., Frotscher, M., Hearing, M., Wickman, K., Watanabe, M., Kulik, A., and Vida, I.
College/School:College of Medical Veterinary and Life Sciences > School of Life Sciences
Journal Name:Journal of Neuroscience
Publisher:Society for Neuroscience
ISSN:0270-6474
ISSN (Online):1529-2401

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