Gjd2b-mediated gap junctions promote glutamatergic synapse formation and dendritic elaboration in Purkinje neurons
Abstract
Gap junctions between neurons serve as electrical synapses, in addition to conducting metabolites and signaling molecules. During development, early-appearing gap junctions are thought to prefigure chemical synapses, which appear much later. We present evidence for this idea at a central, glutamatergic synapse and provide some mechanistic insights. Loss or reduction in the levels of the gap junction protein Gjd2b decreased the frequency of glutamatergic miniature excitatory postsynaptic currents (mEPSCs) in cerebellar Purkinje neurons (PNs) in larval zebrafish. Ultrastructural analysis in the molecular layer showed decreased synapse density. Further, mEPSCs had faster kinetics and larger amplitudes in mutant PNs, consistent with their stunted dendritic arbors. Time-lapse microscopy in wild type and mutant PNs reveals that Gjd2b puncta promote the elongation of branches and that CaMKII may be a critical mediator of this process. These results demonstrate that Gjd2b-mediated gap junctions regulate glutamatergic synapse formation and dendritic elaboration in PNs.
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All data generated or analysed during this study are included in the manuscript and supporting files
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Funding
The Wellcome Trust DBT India Alliance (500040/Z/09/Z and IA/S/17/2/503297)
- Vatsala Thirumalai
Department of Biotechnology, Ministry of Science and Technology, India (BT/PR4983/MED/30/790/2012)
- Vatsala Thirumalai
Science and Engineering Research Board (EMR/2015/000595)
- Vatsala Thirumalai
Department of Atomic Energy, Government of India (12-R&DTFR-5.04-0800)
- Vatsala Thirumalai
Council of Scientific and Industrial Research, India
- Shaista Jabeen
Science and Engineering Research Board (YSS/2015/000908)
- Gnaneshwar Yadav
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: Institutional Animal Ethics and Biosafety committee approvals were obtained for all procedures adopted in this study ( NCB/IAEC/VT-1/2011 and TFR/NCBS/14-IBSC/VT-1/2011). Larvae and adults were reared using standard procedures (Westerfield, 2000).
Copyright
© 2021, Sitaraman et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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