Neuronal Dystroglycan regulates postnatal development of CCK/cannabinoid receptor-1 interneurons

Neural Development

Daniel S. Miller¹  Kevin M. Wright² 

[1] Neuroscience Graduate Program, Oregon Health & Science University, 97239, Portland, OR, USA;Vollum Institute, Oregon Health & Science University, VIB 3435A, 3181 SW Sam Jackson Park Road, L474, 97239-3098, Portland, OR, USA;

关键词: Dystroglycan;    Cannabinoid receptor;    Cholecystokinin;    Interneuron;    Synapse;    Apoptosis;   

DOI  :  10.1186/s13064-021-00153-1

来源: Springer

【 摘 要 】

BackgroundThe development of functional neural circuits requires the precise formation of synaptic connections between diverse neuronal populations. The molecular pathways that allow GABAergic interneuron subtypes in the mammalian brain to initially recognize their postsynaptic partners remain largely unknown. The transmembrane glycoprotein Dystroglycan is localized to inhibitory synapses in pyramidal neurons, where it is required for the proper function of CCK+ interneurons. However, the precise temporal requirement for Dystroglycan during inhibitory synapse development has not been examined.MethodsIn this study, we use NEXCre or Camk2aCreERT2 to conditionally delete Dystroglycan from newly-born or adult pyramidal neurons, respectively. We then analyze forebrain development from postnatal day 3 through adulthood, with a particular focus on CCK+ interneurons.ResultsIn the absence of postsynaptic Dystroglycan in developing pyramidal neurons, presynaptic CCK+ interneurons fail to elaborate their axons and largely disappear from the cortex, hippocampus, amygdala, and olfactory bulb during the first two postnatal weeks. Other interneuron subtypes are unaffected, indicating that CCK+ interneurons are unique in their requirement for postsynaptic Dystroglycan. Dystroglycan does not appear to be required in adult pyramidal neurons to maintain CCK+ interneurons. Bax deletion did not rescue CCK+ interneurons in Dystroglycan mutants during development, suggesting that they are not eliminated by canonical apoptosis. Rather, we observed increased innervation of the striatum, suggesting that the few remaining CCK+ interneurons re-directed their axons to neighboring areas where Dystroglycan expression remained intact.ConclusionTogether these findings show that Dystroglycan functions as part of a synaptic partner recognition complex that is required early for CCK+ interneuron development in the forebrain.

【 授权许可】

CC BY