Distinct homeostatic modulations stabilize reduced postsynaptic receptivity in response to presynaptic DLK signaling

Nat Commun. 2018 May 10;9(1):1856. doi: 10.1038/s41467-018-04270-0.

Abstract

Synapses are constructed with the stability to last a lifetime, yet sufficiently flexible to adapt during injury. Although fundamental pathways that mediate intrinsic responses to neuronal injury have been defined, less is known about how synaptic partners adapt. We have investigated responses in the postsynaptic cell to presynaptic activation of the injury-related Dual Leucine Zipper Kinase pathway at the Drosophila neuromuscular junction. We find that the postsynaptic compartment reduces neurotransmitter receptor levels, thus depressing synaptic strength. Interestingly, this diminished state is stabilized through distinct modulations to two postsynaptic homeostatic signaling systems. First, a retrograde response normally triggered by reduced receptor levels is silenced, preventing a compensatory enhancement in presynaptic neurotransmitter release. However, when global presynaptic release is attenuated, a postsynaptic receptor scaling mechanism persists to adaptively stabilize this diminished neurotransmission state. Thus, the homeostatic set point of synaptic strength is recalibrated to a reduced state as synapses acclimate to injury.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Drosophila / physiology*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • MAP Kinase Kinase Kinases / genetics
  • MAP Kinase Kinase Kinases / metabolism*
  • Neuromuscular Junction / cytology
  • Neuromuscular Junction / metabolism*
  • Neuronal Plasticity / physiology
  • Neurons / physiology
  • Neurotransmitter Agents / metabolism
  • Presynaptic Terminals / metabolism*
  • Receptors, Glutamate / genetics
  • Receptors, Glutamate / metabolism
  • Signal Transduction / physiology
  • Synaptic Potentials / physiology*

Substances

  • Drosophila Proteins
  • Neurotransmitter Agents
  • Receptors, Glutamate
  • MAP Kinase Kinase Kinases
  • mitogen-activated protein kinase kinase kinase 12
  • wnd protein, Drosophila