ArticleEpilepsia2018
Kappa opioid receptors regulate hippocampal synaptic homeostasis and epileptogenesis.
Article in Epilepsia, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 15 citations in OpenAlex.
- Short-chain PFAS exposure during gestation and breastfeeding alters learning and memory in adulthood: possible mechanisms related to brain development.Frontiers in toxicology · 2025Article
- Scoping review of disease-modifying effect of drugs in experimental epilepsy.Frontiers in neurology · 2023Article
- Perinatal Opioid Exposure Results in Persistent Hypoconnectivity of Excitatory Circuits and Reduced Activity Correlations in Mouse Primary Auditory Cortex.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- DREADDs in Epilepsy Research: Network-Based Review.Frontiers in molecular neuroscience · 2022Review
- Hippocampal CA3 transcriptional modules associated with granule cell alterations and cognitive impairment in refractory mesial temporal lobe epilepsy patients.Scientific reports · 2021Article
- Salvinorin A Does Not Affect Seizure Threshold in Mice.Molecules (Basel, Switzerland) · 2020Article
- Homeostatic Plasticity in Epilepsy.Frontiers in cellular neuroscience · 2020Article
- What goes up must come down: homeostatic synaptic plasticity strategies in neurological disease.Future neurology · 2018Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
objectiveHomeostatic synaptic plasticity (HSP) serves as a gain control mechanism at central nervous system (CNS) synapses, including those between the dentate gyrus (DG) and CA3. Improper circuit control of DG-CA3 synapses is hypothesized to underlie epileptogenesis. Here, we sought to (1) identify compounds that preferentially modulate DG-CA3 synapses in primary neuronal culture and (2) determine if these compounds would delay or prevent epileptogenesis in vivo.
methodsWe previously developed and validated an in vitro assay to visualize the behavior of DG-CA3 synapses and predict functional changes. We used this "synapse-on-chip" assay (quantification of synapse size, number, and type using immunocytochemical markers) to dissect the mechanisms of HSP at DG-CA3 synapses. Using chemogenetic constructs and pharmacological agents we determined the signaling cascades necessary for gain control at DG-CA3 synapses. Finally, we tested the implicated cascades (using kappa opioid receptor (OR) agonists and antagonists) in two models of epileptogenesis: electrical amygdala kindling in the mouse and chemical (pentylenetetrazole) kindling in the rat.
resultsIn vitro, synapses between DG mossy fibers (MFs) and CA3 neurons are the primary homeostatic responders during sustained periods of activity change. Kappa OR signaling is both necessary and sufficient for the homeostatic elaboration of DG-CA3 synapses, induced by presynaptic DG activity levels. Blocking kappa OR signaling in vivo attenuates the development of seizures in both mouse and rat models of epilepsy. SIGNIFICANCE: This study elucidates mechanisms by which synapses between DG granule cells and CA3 pyramidal neurons undergo activity-dependent homeostatic compensation, via OR signaling in vitro. Modulation of kappa OR signaling in vivo alters seizure progression, suggesting that breakdown of homeostatic closed-loop control at DG-CA3 synapses contributes to seizures, and that targeting endogenous homeostatic mechanisms at DG-CA3 synapses may prove useful in combating epileptogenesis.
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Registered trials
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