ASC transporters mediate D-serine transport into astrocytes adjacent to synapses in mouse brain

Background: D-serine is an important signaling molecule, which activates N-methyl D-aspartate receptors (NMDARs) in conjunction with its fellow co-agonist, the neurotransmitter glutamate.
Question: Despite its involvement in plasticity and memory related to excitatory synapses, its cellular source and sink remain a question.
Importance: This removal of synaptic D-serine and its subsequent metabolic degradation is expected to reduce its extracellular availability, influencing NMDAR activation and NMDAR-dependent synaptic plasticity.
Hypothesis: We hypothesise that astrocytes, a type of glial cell that surround synapses are likely candidates to control the extracellular concentration of D-Serine by removing it from the synaptic space.
Notable finding: We observed D-serine induced transport-associated currents upon puff-application of 10 mM D-serine on astrocytes. Further, O-benzyl-L-serine and trans-4-hydroxy-proline, known substrate inhibitors of the alanine serine cysteine transporters (ASCT) reduced D-serine uptake. These results indicate that ASCT is a central mediator of astrocytic D-serine transport and plays a role in regulating its synaptic concentration by sequestration into astrocytes. Similar results were observed in astrocytes of the somatosensory cortex and Bergmann glia in the cerebellum, indicative of a general mechanism expressed across a range of brain areas.
How was it gathered: We used patch clamping technique, to study the transmembrane electrical signals from individual identified astrocytes in the CA1 region of hippocampus, primary somatosensory cortex and Bergmann glia. It involved placing a tiny glass patch pipette, onto the surface of the astrocytic membrane, to record D-serine transporter currents.
Methods: Using in situ patch clamp recordings and pharmacological manipulation of astrocytes in CA1 region of the mouse hippocampal brain slices, we investigated transport of D-serine across the plasma membrane.
How to interpret data: The spread sheet contains all the mean astrocytic D-serine currents that were recorded from individual cells.
How to use it: The raw data traces are most compatible with Clampfit 10.7.0.3 (P Clamp - Molecular devices 2016).