Postsynaptic GABABRs Inhibit L-Type Calcium Channels and Abolish Long-Term Potentiation in Hippocampal Somatostatin Interneurons

Abstract

Correspondence akos.kulik@physiologie.uni-freiburg.de (Á .K.), imre.vida@charite. de (I.V.) In Brief Booker et al. show that GABA B receptors are highly expressed on somatostatin interneuron dendrites. Rather than activating Kir3 channels, they preferentially co-cluster with, and negatively couple to, L-type calcium channels inhibiting long-term potentiation at excitatory inputs. Booker et al., 2018, Cell Reports 22, 36- channels on SOM-IN dendrites, leading to reduced calcium influx and loss of long-term potentiation at excitatory input synapses onto these INs. These data provide a mechanism by which GABA B Rs can contribute to disinhibition and control the efficacy of extrinsic inputs to hippocampal networks.

GABAB receptors modulate Ca2+ but not G protein‐gated inwardly rectifying K+ channels in cerebrospinal‐fluid contacting neurones of mouse brainstem

“…; Booker et al . ). Consistent with the literature, we demonstrate in medullar CSF‐cNs that GABA B ‐Rs strongly and selectively inhibit Ca V 2.2 and we show that this inhibition is mediated by a voltage‐dependent Gβγ mechanism.…”

“…) ionic conductance and/or of regulating postsynaptic receptors through Ca 2+ ‐dependent phosphorylation processes (Booker et al . ). Similar mechanisms might exist in CSF‐cNs to regulate their activity and excitability.…”

“…; Booker et al . ). Finally, GABA B ‐Rs can influence pre‐ and postsynaptic functions by inhibiting adenylyl cyclase, though the physiological consequences of this modulation are poorly understood (Padgett & Slesinger, ).…”

Integrated Transcriptome Analyses Revealed Key Target Genes in Mouse Models of Autism

“…Similar to the results of the cortex‐adult group, many of the overlapped DEGs play important roles in the structure and function of synapses. Moreover, some other enriched processes including neural circuits formation, intracellular calcium dysregulation and calcium‐dependent pathways, have also been associated with ASD [Booker et al, ]. Therefore, misregulation of these overlapped DEGs and the related biological processes in the developing cortex may contribute to the pathology of ASD.…”

“…These biological processes have been reported to be essential for various aspects of the nervous system, such as neurodevelopment, behavior, synaptic plasticity, axon pathfinding, and so forth, many of which have been associated with ASD. Interestingly, dysfunction of mitochondria, calcium and MAPK and cAMP signaling pathway have been reported to associate with abnormal synaptic plasticity [Fernandez et al, ; Booker et al, ; Vithayathil, Pucilowska, & Landreth, ; Cui et al, ; Zamarbide et al, ]. It is possible that the different transcriptional factors may result in ASD by the final dysfunction of synapses.…”