Autocrine signaling by an Aplysia neurotrophin forms a presynaptic positive feedback loop

Proc Natl Acad Sci U S A. 2018 Nov 20;115(47):E11168-E11177. doi: 10.1073/pnas.1810649115. Epub 2018 Nov 5.

Abstract

Whereas short-term plasticity is often initiated on one side of the synapse, long-term plasticity involves coordinated changes on both sides, implying extracellular signaling. We have investigated the possible signaling role of an Aplysia neurotrophin (ApNT) in facilitation induced by serotonin (5HT) at sensory-to-motor neuron synapses in culture. ApNT is an ortholog of mammalian BDNF, which has been reported to act as either an anterograde, retrograde, or autocrine signal, so that its pre- and postsynaptic sources and targets remain unclear. We now report that ApNT acts as a presynaptic autocrine signal that forms part of a positive feedback loop with ApTrk and PKA. That loop stimulates spontaneous transmitter release, which recruits postsynaptic mechanisms, and presynaptic protein synthesis during the transition from short- to intermediate-term facilitation and may also initiate gene regulation to trigger the transition to long-term facilitation. These results suggest that a presynaptic ApNT feedback loop plays several key roles during consolidation of learning-related synaptic plasticity.

Keywords: Aplysia; autocrine; facilitation; neurotrophin; presynaptic.

Publication types

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

MeSH terms

  • Animals
  • Aplysia / physiology*
  • Autocrine Communication / physiology*
  • Cyclic AMP-Dependent Protein Kinases / metabolism*
  • Excitatory Postsynaptic Potentials / physiology
  • Long-Term Potentiation / physiology
  • Motor Neurons / physiology
  • Nerve Growth Factors / metabolism*
  • Neuronal Plasticity / physiology
  • Presynaptic Terminals / physiology
  • Receptor Protein-Tyrosine Kinases / metabolism*
  • Sensory Receptor Cells / physiology
  • Serotonin / metabolism
  • Serotonin Plasma Membrane Transport Proteins / metabolism
  • Signal Transduction / physiology
  • Synapses / physiology*

Substances

  • Nerve Growth Factors
  • Serotonin Plasma Membrane Transport Proteins
  • Serotonin
  • Receptor Protein-Tyrosine Kinases
  • Cyclic AMP-Dependent Protein Kinases