Abstract
In the past, the spontaneous release of neurotransmitter from presynaptic terminals has been thought of as a side effect of evoked release, with little functional significance. As our understanding of the process of spontaneous release has increased over time, this notion has gradually changed. In this review, we focus on the importance of this form of release during neuronal development, a time of extreme levels of plasticity that includes the growth of dendrites and axons as well as the formation of new synaptic contacts. This period also encompasses high levels of neurotransmitter release from growing axons, and recent studies have found that spontaneous transmitter release plays an important role in shaping neuronal morphology as well as modulating the properties of newly forming synaptic contacts in the brain. Here, we bring together the latest findings across different species to argue that the spontaneous release of neurotransmitter is an important player in the wiring of the brain during development.
Highlights
We focus on the importance of this form of release during neuronal development, a time of extreme levels of plasticity that includes the growth of dendrites and axons as well as the formation of new synaptic contacts
To examine levels of spontaneous release directly at individual boutons, fluorescent reporters of vesicle exocytosis have been used to integrate the total number of release events over long periods of time, in the absence of any activity. One such reporter of presynaptic vesicle exocytosis, biosyn, is well suited to independently report both evoked and spontaneous vesicle cycling within the same presynaptic bouton, with different colors (Fredj & Burrone, 2009). Using this tool in cultured rat hippocampal neurons evoked release was found to increase with development in a manner similar to that previously observed (Mozhayeva et al, 2002), but spontaneous vesicle cycling was found to occur at exceptionally high levels in young neurons, which progressively decreased with maturation (Andreae, Fredj, & Burrone, 2012)
The fact that developing mammalian central nervous system (CNS) neurons exhibit very high levels of spontaneous synaptic vesicle cycling, in the absence of evoked release early on, suggests that spontaneous release has an important role to play during development
Summary
We focus on the importance of this form of release during neuronal development, a time of extreme levels of plasticity that includes the growth of dendrites and axons as well as the formation of new synaptic contacts. This period encompasses high levels of neurotransmitter release from growing axons, and recent studies have found that spontaneous transmitter release plays an important role in shaping neuronal morphology as well as modulating the properties of newly forming synaptic contacts in the brain.
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