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

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).