α2δ-2 mediates coupling of presynaptic calcium entry to vesicle release in hippocampal parvalbumin-expressing interneurons
- 1Oregon Health & Science University
Abstract
The 2{delta} family of auxiliary voltage-gated calcium channel (VGCC) subunits have critical but incompletely understood roles in brain function. Parvalbumin-positive (PV+) interneurons in the hippocampus highly express the 2{delta}-2 isoform, and mice lacking 2{delta}-2 exhibit spontaneous seizures. Thus, we examined PV+ neuron-mediated synaptic inhibition in acutely prepared brain slices from 2{delta}-2 knockout (KO) mice. In the inner molecular layer of the dentate gyrus, 2{delta}-2 KO mice demonstrated an increase in the excitation/inhibition ratio of synaptic inputs onto granule cells. We then used optogenetics to activate PV+ interneurons, which produced dramatically smaller inhibitory synaptic currents in granule cells from 2{delta}-2 KO mice. There was a reduction in PV+ inputs onto granule cells as determined by immunostaining. Functionally, these inputs had a lower probability of GABA release and a decreased readily releasable pool of vesicles compared to littermate controls. VGCC coupling to presynaptic vesicle release was also reduced in dentate gyrus PV+ cells in 2{delta}-2 KO mice, based on manipulations of intracellular and extracellular calcium. Together, our data indicate that 2{delta}-2 plays a critical role in PV+ interneuron-mediated synaptic inhibition, which may contribute to seizures in 2{delta}-2 mutant mice.
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BibTeX
@misc{ellingson2026α2δ2,
title = {{α2δ-2 mediates coupling of presynaptic calcium entry to vesicle release in hippocampal parvalbumin-expressing interneurons}},
author = {A. J. Ellingson and E. C. Jerome and A. A. Gallagher and E. Schnell},
howpublished = {bioRxiv},
year = {2026},
month = aug,
doi = {10.64898/2026.08.31.748347},
url = {https://www.biorxiv.org/content/10.64898/2026.08.31.748347v1},
note = {CC0},
}
RIS
TY - UNPB
TI - α2δ-2 mediates coupling of presynaptic calcium entry to vesicle release in hippocampal parvalbumin-expressing interneurons
AU - A. J. Ellingson
AU - E. C. Jerome
AU - A. A. Gallagher
AU - E. Schnell
PY - 2026
DA - 2026/08/31
PB - bioRxiv
DO - 10.64898/2026.08.31.748347
UR - https://www.biorxiv.org/content/10.64898/2026.08.31.748347v1
AB - The 2{delta} family of auxiliary voltage-gated calcium channel (VGCC) subunits have critical but incompletely understood roles in brain function. Parvalbumin-positive (PV+) interneurons in the hippocampus highly express the 2{delta}-2 isoform, and mice lacking 2{delta}-2 exhibit spontaneous seizures. Thus, we examined PV+ neuron-mediated synaptic inhibition in acutely prepared brain slices from 2{delta}-2 knockout (KO) mice. In the inner molecular layer of the dentate gyrus, 2{delta}-2 KO mice demonstrated an increase in the excitation/inhibition ratio of synaptic inputs onto granule cells. We then used optogenetics to activate PV+ interneurons, which produced dramatically smaller inhibitory synaptic currents in granule cells from 2{delta}-2 KO mice. There was a reduction in PV+ inputs onto granule cells as determined by immunostaining. Functionally, these inputs had a lower probability of GABA release and a decreased readily releasable pool of vesicles compared to littermate controls. VGCC coupling to presynaptic vesicle release was also reduced in dentate gyrus PV+ cells in 2{delta}-2 KO mice, based on manipulations of intracellular and extracellular calcium. Together, our data indicate that 2{delta}-2 plays a critical role in PV+ interneuron-mediated synaptic inhibition, which may contribute to seizures in 2{delta}-2 mutant mice.
ER -