ASC Transporters Mediate D-Serine Transport into Astrocytes Adjacent to Synapses in the Mouse Brain.

D-serine is an important signalling molecule, which activates N-methyl D-aspartate receptors (NMDARs) in conjunction with its fellow co-agonist, the neurotransmitter glutamate. Despite its involvement in plasticity and memory related to excitatory synapses, its cellular source and sink remain a question. We hypothesise that astrocytes, a type of glial cell that surrounds synapses, are likely candidates to control the extracellular concentration of D-Serine by removing it from the synaptic space.

PKC-Mediated Modulation of Astrocyte SNAT3 Glutamine Transporter Function at Synapses in Situ.

Astrocytes are glial cells that have an intimate physical and functional association with synapses in the brain. One of their main roles is to recycle the neurotransmitters glutamate and gamma-aminobutyric acid (GABA), as a component of the glutamate/GABA-glutamine cycle. They perform this function by sequestering neurotransmitters and releasing glutamine via the neutral amino acid transporter SNAT3.

SNAT3-mediated glutamine transport in perisynaptic astrocytes in situ is regulated by intracellular sodium.

The release of glutamine from astrocytes adjacent to synapses in the central nervous system is thought to play a vital role in the mechanism of glutamate recycling and is therefore important for maintaining excitatory neurotransmission. Here we investigate the nature of astrocytic membrane transport of glutamine in rat brainstem slices, using electrophysiological recording and fluorescent imaging of pH and Nai+. Glutamine application to perisynaptic astrocytes induced a membrane current, caused by activation of system A (SA) family transporters.

Astrocyte sodium signaling and the regulation of neurotransmission.

The transmembrane Na(+) concentration gradient is an important source of energy required not only to enable the generation of action potentials in excitable cells, but also for various transmembrane transporters both in excitable and non-excitable cells, like astrocytes. One of the vital functions of astrocytes in the central nervous system (CNS) is to regulate neurotransmitter concentrations in the extracellular space. Most neurotransmitters in the CNS are removed from the extracellular space by Na(+) -dependent neurotransmitter transporters (NeuTs) expressed both in neurons and astrocytes.

Maintaining the presynaptic glutamate supply for excitatory neurotransmission.

Glutamate released from synapses during excitatory neurotransmission must be rapidly recycled to maintain neuronal communication. This review evaluates data from physiological experiments at hippocampal CA3 to CA1 synapses and the calyx of Held synapse in the brainstem to analyze quantitatively the rates of release and resupply of glutamate required to sustain neurotransmission. We calculate that, without efficient recycling, the presynaptic glutamate supply will be exhausted within about a minute of normal synaptic activity.