{"title":"Somatostatin Interneurons Recruit Pre- and Postsynaptic GABA<sub>B</sub> Receptors in the Adult Mouse Dentate Gyrus.","authors":"Thomas C Watson, Sam A Booker","doi":"10.1523/ENEURO.0115-24.2024","DOIUrl":null,"url":null,"abstract":"<p><p>The integration of spatial information in the mammalian dentate gyrus (DG) is critical to navigation. Indeed, DG granule cells (DGCs) rely upon finely balanced inhibitory neurotransmission in order to respond appropriately to specific spatial inputs. This inhibition arises from a heterogeneous population of local GABAergic interneurons (INs) that activate both fast, ionotropic GABA<sub>A</sub> receptors (GABA<sub>A</sub>R) and slow, metabotropic GABA<sub>B</sub> receptors (GABA<sub>B</sub>R), respectively. GABA<sub>B</sub>Rs in turn inhibit pre- and postsynaptic neuronal compartments via temporally long-lasting G-protein-dependent mechanisms. The relative contribution of each IN subtype to network level GABA<sub>B</sub>R signal setting remains unknown. However, within the DG, the somatostatin (SSt) expressing IN subtype is considered crucial in coordinating appropriate feedback inhibition on to DGCs. Therefore, we virally delivered channelrhodopsin 2 to the DG in order to obtain control of this specific SSt IN subpopulation in male and female adult mice. Using a combination of optogenetic activation and pharmacology, we show that SSt INs strongly recruit postsynaptic GABA<sub>B</sub>Rs to drive greater inhibition in DGCs than GABA<sub>A</sub>Rs at physiological membrane potentials. Furthermore, we show that in the adult mouse DG, postsynaptic GABA<sub>B</sub>R signaling is predominantly regulated by neuronal GABA uptake and less so by astrocytic mechanisms. Finally, we confirm that activation of SSt INs can also recruit presynaptic GABA<sub>B</sub>Rs, as has been shown in neocortical circuits. Together, these data reveal that GABA<sub>B</sub>R signaling allows SSt INs to control DG activity and may constitute a key mechanism for gating spatial information flow within hippocampal circuits.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":null,"pages":null},"PeriodicalIF":2.7000,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11334949/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"eNeuro","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1523/ENEURO.0115-24.2024","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/8/1 0:00:00","PubModel":"Print","JCR":"Q3","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
引用次数: 0
Abstract
The integration of spatial information in the mammalian dentate gyrus (DG) is critical to navigation. Indeed, DG granule cells (DGCs) rely upon finely balanced inhibitory neurotransmission in order to respond appropriately to specific spatial inputs. This inhibition arises from a heterogeneous population of local GABAergic interneurons (INs) that activate both fast, ionotropic GABAA receptors (GABAAR) and slow, metabotropic GABAB receptors (GABABR), respectively. GABABRs in turn inhibit pre- and postsynaptic neuronal compartments via temporally long-lasting G-protein-dependent mechanisms. The relative contribution of each IN subtype to network level GABABR signal setting remains unknown. However, within the DG, the somatostatin (SSt) expressing IN subtype is considered crucial in coordinating appropriate feedback inhibition on to DGCs. Therefore, we virally delivered channelrhodopsin 2 to the DG in order to obtain control of this specific SSt IN subpopulation in male and female adult mice. Using a combination of optogenetic activation and pharmacology, we show that SSt INs strongly recruit postsynaptic GABABRs to drive greater inhibition in DGCs than GABAARs at physiological membrane potentials. Furthermore, we show that in the adult mouse DG, postsynaptic GABABR signaling is predominantly regulated by neuronal GABA uptake and less so by astrocytic mechanisms. Finally, we confirm that activation of SSt INs can also recruit presynaptic GABABRs, as has been shown in neocortical circuits. Together, these data reveal that GABABR signaling allows SSt INs to control DG activity and may constitute a key mechanism for gating spatial information flow within hippocampal circuits.
期刊介绍:
An open-access journal from the Society for Neuroscience, eNeuro publishes high-quality, broad-based, peer-reviewed research focused solely on the field of neuroscience. eNeuro embodies an emerging scientific vision that offers a new experience for authors and readers, all in support of the Society’s mission to advance understanding of the brain and nervous system.