Synaptic Vesicle Pools and Dynamics

Abstract

Synaptic vesicles release neurotransmitter at chemical synapses, thus initiating the flow of information in neural networks. To achieve this, vesicles undergo a dynamic cycle of fusion and retrieval to maintain the structural and functional integrity of the presynaptic terminals in which they reside. Moreover, compelling evidence indicates these vesicles differ in their availability for release and mobilization in response to stimuli, prompting classification into at least three different functional pools. Ongoing studies of the molecular and cellular bases for this heterogeneity attempt to link structure to physiology and clarify how regulation of vesicle pools influences synaptic strength and presynaptic plasticity. We discuss prevailing perspectives on vesicle pools, the role they play in shaping synaptic transmission, and the open questions that challenge current understanding.

Replacement of microglia in the aged brain reverses cognitive, synaptic, and neuronal deficits in mice

“…In accordance with the restoration of gene expression changes, microglial elimination and repopulation restored age‐related reductions in neuronal complexities to those found in the young brain, while also modulating dendritic spine densities. Crucially, actin cytoskeleton remodeling is highly associated with synaptic plasticity and memory (Lamprecht, 2014), as is synaptic vesicle release (Alabi & Tsien, 2012), and we found that microglial replacement fully restores LTP, the synaptic mechanism underlying memory formation, in 24‐month‐old mice to levels comparable to 4‐month‐old mice.…”

Ultrastructural readout of functional synaptic vesicle pools in hippocampal slices based on FM dye labeling and photoconversion

“…The presynaptic terminal is characterized by a cluster of neurotransmitter-containing synaptic vesicles and transmission proceeds with their activity-driven fusion leading to the discharge of chemical transmitter towards postsynaptic receptors. While vesicles appear morphologically equivalent they can be sub-divided into pools on the basis of their functional behaviour, including a recycling pool (see 2,3 , readilyreleasable pool 4 , spontaneous pool 5,6 and superpool 7,8 . Understanding the properties of these pools has become increasingly important with the realization that they are potentially critical substrates in setting synaptic strength 9,10 and represent modifiable targets on which forms of plasticity 9,[11][12][13][14] or disease-like conditions [15][16][17] might act to modulate or disrupt information flow.…”

Quantitative analysis of vesicle recycling at the calyx of Held synapse

“…The use of vesicles in recycling is a critical determinant of synaptic transmission (1,(13)(14)(15). However, it has never been rigorously determined how fast recently recaptured vesicles are organized to recycle and whether vesicles in the RP are homogeneously ready for use (25).…”

“…The resting pool serves as a depot of vesicles for backup use (16,22). However, it has been debated for a decade whether nerve terminals use the majority (∼100%, from electrophysiology) or only a small fraction (5-40%, from fluorescence imaging and EM) of vesicles in recycling, and whether the RP size undergoes dynamic changes during varied neuronal activity (6,7,(23)(24)(25)(26)(27)(28).The use of vesicles in recycling is a critical determinant of synaptic transmission (1,(13)(14)(15). However, it has never been rigorously determined how fast recently recaptured vesicles are organized to recycle and whether vesicles in the RP are homogeneously ready for use (25).…”

“…kinetics | vesicle recycling | vesicle pool | calyx of Held | short-term plasticity S ynaptic vesicle recycling ensures synaptic transmission during sustained neuronal activity (1)(2)(3). Despite its crucial role, the cycle is poorly understood.…”