PT - JOURNAL ARTICLE AU - Jyoti Gupta AU - Mark Bromwich AU - Jake Radell AU - Muhammad N Arshad AU - Selena Gonzalez AU - Bryan W Luikart AU - Gloster B Aaron AU - Janice R Naegele TI - Restrained Dendritic Growth of Adult-born Granule Cells Innervated by Transplanted Fetal GABAergic Interneurons in Mice with Temporal Lobe Epilepsy AID - 10.1523/ENEURO.0110-18.2019 DP - 2019 Mar 27 TA - eneuro PG - ENEURO.0110-18.2019 4099 - http://www.eneuro.org/content/early/2019/03/22/ENEURO.0110-18.2019.short 4100 - http://www.eneuro.org/content/early/2019/03/22/ENEURO.0110-18.2019.full AB - The dentate gyrus (DG) is a region of the adult rodent brain that undergoes continuous neurogenesis. Seizures and loss or dysfunction of GABAergic synapses onto adult-born dentate granule cells (GCs) alter their dendritic growth and migration, resulting in dysmorphic and hyperexcitable GCs. Additionally, transplants of fetal GABAergic interneurons in the DG of mice with temporal lobe epilepsy (TLE) result in seizure suppression, but it is unknown whether increasing interneurons with these transplants restores GABAergic innervation to adult-born GCs. Here we address this question by retroviral birth-dating GCs at different times up to 12 weeks after pilocarpine-induced TLE in adult mice. ChR2-EYFP-expressing MGE-derived GABAergic interneurons from E13.5 mouse embryos were transplanted into the DG of the TLE mice and GCs with transplant-derived inhibitory post-synaptic currents were identified by patch-clamp electrophysiology and optogenetic interrogation. Putative synaptic sites between GCs and GABAergic transplants were also confirmed by intracellular biocytin staining, immunohistochemistry, and confocal imaging. 3D reconstructions of dendritic arbors and quantitative morphometric analyses were carried out in >150 adult-born GCs. GABAergic inputs from transplanted interneurons correlated with markedly shorter GC dendrites, compared to GCs that were not innervated by the transplants. Moreover, these effects were confined to distal dendritic branches and a short time window of 6-8 weeks. The effects were independent of seizures as they were also observed in naïve mice with MGE transplants. These findings are consistent with the hypothesis that increased inhibitory currents over a smaller dendritic arbor in adult-born GCs may reduce their excitability and lead to seizure suppression.Significance statement Transplants of medial-ganglionic eminence (MGE) GABAergic progenitors into the hippocampus of adult mice with pilocarpine-induced TLE have been shown to increase inhibitory synaptic currents in granule cells (GCs) in the dentate gyrus (DG) and suppress seizures. Here we investigated whether the increased transplant-derived inhibition resulted in structural changes to the dendritic arbors of adult-born GCs that might be responsible for reduced excitability. Our results show that transplant-innervated adult-born GCs form significantly shorter dendrites compared to non-innervated GCs. These changes were restricted to distal dendrites in GCs generated within two-months after transplantation. These findings suggest a structural mechanism for seizure suppression whereby increased GABAergic innervation from transplanted MGE progenitors may restrict the growth of dendritic arbors in adult-born hippocampal granule cells.