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PSD93 regulates synaptic stability at neuronal cholinergic synapses.

Michael J Parker1, Shengli Zhao, David S Bredt

  • 1Department of Neurobiology, Duke University Medical Center, Durham, North Carolina 27710, USA.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
|January 16, 2004
PubMed
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Postsynaptic density 93 (PSD93) is crucial for stabilizing neuronal cholinergic synapses. While synapses form normally without PSD93, they disassemble faster after denervation, highlighting PSD93

Area of Science:

  • Neuroscience
  • Synaptic Biology
  • Molecular Cell Biology

Background:

  • Neuronal cholinergic synapses are vital in the peripheral and central nervous systems.
  • Mechanisms governing the formation, maturation, and stability of these synapses remain largely unknown.
  • Understanding postsynaptic complex assembly is key to elucidating synaptic function and regulation.

Purpose of the Study:

  • To investigate the molecular components and functional role of the postsynaptic complex in neuronal cholinergic synapses.
  • To examine the expression and localization of postsynaptic density 93 (PSD93) in cholinergic synapses.
  • To determine the contribution of PSD93 to the stability of neuronal cholinergic synapses.

Main Methods:

  • Utilized mouse superior cervical ganglion (SCG) and submandibular ganglion (SMG) models.

Related Experiment Videos

  • Employed immunostaining, subcellular fractionation, and coimmunoprecipitation techniques.
  • Analyzed PSD93 null mice to assess synaptic stability following denervation.

    • Main Results:

    • Identified novel splicing forms of PSD93 expressed in SCG.
    • Demonstrated precise colocalization and in vivo complex formation of PSD93 with neuronal nicotinic acetylcholine receptors (nAChRs).
    • Found that PSD93 null mice exhibit accelerated disassembly of nAChR clusters after denervation, despite normal synapse formation.

    Conclusions:

    • PSD93 is a critical component of the postsynaptic scaffold in neuronal cholinergic synapses.
    • PSD93 plays a significant role in maintaining the stability of these synapses.
    • Suggests conserved postsynaptic scaffolding mechanisms between cholinergic and glutamatergic synapses.