White matter (WM) tracts are bundles of myelinated axons that provide for rapid communication throughout the CNS and integration in grey matter (GM). The main cells in myelinated tracts are oligodendrocytes and astrocytes, with small populations of microglia and oligodendrocyte precursor cells. The prominence of neurotransmitter signaling in WM, which largely exclude neuronal cell bodies, indic...

I t is well established that calcium is the trigger for fast action potentialevoked synaptic transmission (1). After elevation of intracellular calcium ([Ca2 ]i) by action potential-mediated opening of voltage-dependent calcium channels (VDCCs), a low resting rate of neurotransmitter release of 0.01–0.03 vesicles per sec is elevated significantly to 20 per sec (2–4). Transmitter release occurri...

The synaptic vesicle cycle can now be subdivided into a series of defined steps. These are the tethering of the SSV at the active site of the presynaptic membrane, followed by docking and by an ATP-dependent phase, termed priming. Fusion of the primed SSV with the plasma membrane is triggered by CA2+ entry through specific Ca2+ channels. All the steps in the SSV life cycle are regulated through...

The discovery of glutamate (Glu) is more than 100 years old, dating from when Ikeda isolated this natural amino acid from seaweed broth. Discoveries of neurotransmitter function, the role of Glu as a neurotransmitter, and Glu receptors and receptor types and functions followed over the subsequent century. To date, it is well established that Glu is the major neurotransmitter in the mammalian br...

The vesicular monoamine transporter (VMAT) is a membrane-embedded protein that transports monoamine neurotransmitter molecules into intraneuronal storage vesicles to allow subsequent release into the synapse.1,2 By accumulating both newly synthesized neurotransmitter molecules and freshly returned neurotransmitter molecules from the synapse, VMAT function plays a critical role in the signaling ...