Skip to main content
eScholarship
Open Access Publications from the University of California

UCSF

UC San Francisco Electronic Theses and Dissertations bannerUCSF

Mechanisms of Short Term Plasticity in Presynaptic Homeostatic Plasticity

  • Author(s): Ortega, Jennifer Maria;
  • Advisor(s): Davis, Graeme W;
  • et al.
Abstract

Presynaptic homeostatic plasticity (PHP) compensates for impaired postsynaptic neurotransmitter receptor function through a rapid, persistent adjustment of neurotransmitter release, an effect that can exceed 200%. An unexplained property of PHP is the preservation of short-term plasticity (STP), thereby stabilizing activity-dependent synaptic information transfer. This dissertation aims to understand the mechanisms that stabilize STP during PHP. We use a combination of electrophysiology, genetics, and biochemistry at the Drosophila NMJ to answer this question. We demonstrate that the dramatic potentiation of presynaptic release during PHP is achieved while simultaneously maintaining a constant ratio of primed to super-primed synaptic vesicles, thereby preserving STP. Mechanistically, genetic, biochemical and electrophysiological evidence argue that a constant ratio of primed to super-primed synaptic vesicles is achieved by the concerted action of three proteins: Unc18, Syntaxin1A and RIM. Our data support a model based on the regulated availability of Unc18 at the presynaptic active zone, a process that is restrained by Syntaxin1A and facilitated by RIM. As such, regulated vesicle priming/super-priming enables PHP to stabilize both synaptic gain and the activity-dependent transfer of information at a synapse.

Main Content
For improved accessibility of PDF content, download the file to your device.
Current View