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bioRxiv · 10.1101/741140

GABAA receptors are selectively expressed in NG2 glia of the cerebellar white matter

Labrada-Moncada, E.·Reyes-Haro, D.·Martinez-Torres, A.
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Abstract

The cerebellum is involved in the coordination of movement. Its cellular composition is dominated by GABAergic neuronal types, and glial cells are known to express functional receptors. GABAergic signaling regulates cell proliferation, differentiation, and migration during neurodevelopment. However, little is known about the functional expression of GABA receptors in the cerebellar white matter (WM). Thus, the aim of this study was to test whether glial cells express functional GABA receptors during postnatal development (P7-P9) of cerebellar WM. Immunofluorescence studies showed that half of the astrocytes express GAD67, suggesting that GABA is synthetized by glial cells. Calcium imaging in cerebellar slices revealed that GABA and the GABAA agonist muscimol evoked calcium transients in sulforhodamine B (SRB) negative cells, whereas the GABAB agonist baclofen failed to evoke responses in cerebellar WM. Whole-cell patch-clamp recordings of GFAP+ cells showed dye coupling and a passive current-voltage relation typical of astrocytes. Surprisingly, these cells did not respond to muscimol. Two additional populations were identified as GFAP- cells. The first population showed dye coupling, slow decaying inward and outward currents with no voltage dependence and did not respond to GABAA agonists. The second population showed an outward-rectifying current-voltage relationship and responded to muscimol, but dye coupling was absent. These cells received synaptic input and were NG2+, but evoked calcium waves failed to modulate the frequency of sPSCs or signal directly to NG2 glia. We conclude that GABAA receptor-mediated signaling is selective for NG2 glia in the WM of the cerebellum.

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Labrada-Moncada, E., Reyes-Haro, D., Martinez-Torres, A.. 2019-08-20. GABAA receptors are selectively expressed in NG2 glia of the cerebellar white matter. https://doi.org/10.1101/741140

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