Cortactin controls morphological and electrophysiological properties during activity‐dependent synaptic plasticity at the Drosophila neuromuscular junction

Abstract

In the nervous system, changes in activity that lead to modifications in synaptic structure and function are referred to as synaptic plasticity and are thought to be the basis of learning and memory. Such modifications can be studied at the Drosophila neuromuscular junction (NMJ); a model used to decipher the molecular mechanisms underlying activity‐dependent synaptic plasticity. Recent work has shown that, after repeated stimulations, de novo synaptic structures form at the NMJ and an increase in the frequency of spontaneous release occurs. While the secreted molecule Wingless (Wg)/Wnt was shown to underlie the structural and electrophysiological changes during activity‐dependent plasticity at the NMJ, a challenge remains to understand how this signal mediates the cellular changes that lead to plasticity.In this work, we investigate the role of the actin regulator Cortactin (Cttn) in activity‐dependent synaptic plasticity. With confocal microscopy, we show that Cttn is present at the NMJ, pre and postsynaptically. Also, we show that the synaptic structures that are formed during synaptic plasticity are dependent on presynaptic Cttn expression. In addition, our electrophysiological recordings show that Cttn‐deficient NMJs have a significant reduction in the frequency of spontaneous release. Such reduction can only be rescued by the presynaptic expression of Cttn, which suggests that the neuronal expression of Cttn is necessary for maintaining the rate of spontaneous vesicle fusion at the NMJ. Moreover, presynaptic Cttn is required for the potentiation of spontaneous release that occurs after activity‐dependent synaptic plasticity. Indeed, there is no potentiation of spontaneous release in Cttn mutants and in NMJs depleted of presynaptic Cttn. However, this potentiation is achieved if Cttn is expressed presynaptically in Cttn mutants, or if Cttn is removed only postsynaptically. We argue that presynaptic Cttn is responsible for the structural and/or functional changes affecting active zones during activity‐dependent synaptic plasticity. Overall, our findings suggest that Cttn is an important regulator of structural and physiological synaptic properties in response to activity.Support or Funding InformationThis work was supported by the NIGMS 1P20GM103642 grant to BM and MP; NINDS SC2NS077924 and NSF HRD‐1137725 to BM. Work supported by NIMHD 8G12‐MD007600 RCMI grant. CD and CM received support from NIGMS RISE grant R25GM061838. MP received support from NIGMS RISE grant R25GM06115115.