Three Pools of Synaptic Vesicles Loaded with Neurotransmitter Are Present in the Presynaptic Terminal

A highly organized arrangement of cytoskeletal fibers in the axon terminus helps localize synaptic vesicles within the presynaptic terminal. The population of synaptic vesicles has been proposed to exist in three states: a small readily releasable pool, which is docked at the active zone near the plasma membrane; a larger recycling pool, which is proximal but not docked at the plasma membrane and is released with moderate stimulation; and a reserve pool, which includes the majority of synaptic vesicles in the terminal, is the most distal from the active zone, and is released only in response to strong stimuli. A family of phosphoproteins called synapsins tether synaptic vesicles to the actin cytoskeleton and to one another. Neuronal stimulation activates kinases that phosphorylate synapsins to modulate synaptic vesicle tethering and thereby alter the number of synaptic vesicles available for release. Indeed, synapsin knockout mice, although viable, are prone to seizures; during repetitive stimulation of many neurons in such mice, the number of synaptic vesicles that fuse with the plasma membrane is greatly reduced.