Abstract
Homeostatic plasticity is a process by which neurons adapt to the overall network activity to keep their firing rates in a reasonable range. At the cellular level this kind of plasticity comprises modulation of cellular excitability and tuning of synaptic strength. In this review we concentrate on presynaptic homeostatic plasticity controlling the efficacy of neurotransmitter release from presynaptic boutons. While morphological and electrophysiological approaches were successful to describe homeostatic plasticity-induced changes in the presynaptic architecture and function, cellular and molecular mechanisms underlying those modifications remained largely unknown for a long time. We summarize the latest progress made in the understanding of homeostasis-induced regulation of different steps of the synaptic vesicle cycle and the molecular machineries involved in this process. We particularly focus on the role of presynaptic scaffolding proteins, which functionally and spatially organize synaptic vesicle clusters, neurotransmitter release sites and the associated endocytic machinery. These proteins turned out to be major presynaptic substrates for remodeling during homeostatic plasticity. Finally, we discuss cellular processes and signaling pathways acting during homeostatic molecular remodeling and their potential involvement in the maladaptive plasticity occurring in multiple neuropathologic conditions such as neurodegeneration, epilepsy and neuropsychiatric disorders.
Highlights
Brain function is based on signal transmission between neurons assembled in complex networks
We summarize the latest progress made in the understanding of homeostasis-induced regulation of different steps of the synaptic vesicle cycle and the molecular machineries involved in this process
Neurotransmitter is stored in synaptic vesicles (SVs), which can release their content by controlled fusion with a specialized region of the presynaptic membrane named active zone (AZ)
Summary
Brain function is based on signal transmission between neurons assembled in complex networks. Several studies reported regulation of expression levels of synaptic proteins during presynaptic homeostatic adaptation to alterations in global network activity (Thiagarajan et al, 2005; Cohen et al, 2011; Lazarevic et al, 2011; Weyhersmuller et al, 2011).
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