Differential GABAB-receptor-mediated effects in perisomatic- and dendrite-targeting parvalbumin interneurons
Standard
Differential GABAB-receptor-mediated effects in perisomatic- and dendrite-targeting parvalbumin interneurons. / Booker, Sam A; Gross, Anna; Althof, Daniel; Shigemoto, Ryuichi; Bettler, Bernhard; Frotscher, Michael; Hearing, Matthew; Wickman, Kevin; Watanabe, Masahiko; Kulik, Ákos; Vida, Imre.
In: J NEUROSCI, Vol. 33, No. 18, 01.05.2013, p. 7961-74.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Differential GABAB-receptor-mediated effects in perisomatic- and dendrite-targeting parvalbumin interneurons
AU - Booker, Sam A
AU - Gross, Anna
AU - Althof, Daniel
AU - Shigemoto, Ryuichi
AU - Bettler, Bernhard
AU - Frotscher, Michael
AU - Hearing, Matthew
AU - Wickman, Kevin
AU - Watanabe, Masahiko
AU - Kulik, Ákos
AU - Vida, Imre
PY - 2013/5/1
Y1 - 2013/5/1
N2 - 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.
AB - 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.
KW - Animals
KW - Animals, Newborn
KW - Axons
KW - Cholecystokinin
KW - Computer Simulation
KW - Dendrites
KW - G Protein-Coupled Inwardly-Rectifying Potassium Channels
KW - GABA Agents
KW - Green Fluorescent Proteins
KW - Hippocampus
KW - Inhibitory Postsynaptic Potentials
KW - Interneurons
KW - Male
KW - Models, Neurological
KW - Neural Inhibition
KW - Neuropeptide Y
KW - Nipecotic Acids
KW - Parvalbumins
KW - Rats
KW - Rats, Transgenic
KW - Rats, Wistar
KW - Receptors, GABA-B
KW - Vesicular Inhibitory Amino Acid Transport Proteins
KW - gamma-Aminobutyric Acid
U2 - 10.1523/JNEUROSCI.1186-12.2013
DO - 10.1523/JNEUROSCI.1186-12.2013
M3 - SCORING: Journal article
C2 - 23637187
VL - 33
SP - 7961
EP - 7974
JO - J NEUROSCI
JF - J NEUROSCI
SN - 0270-6474
IS - 18
ER -