Inositol 1,4,5-trisphosphate signaling maintains the activity of glutamate uptake in Bergmann glia

• Published in: The European journal of neuroscience Vol. 32; no. 10; pp. 1668 - 1677
• Main Authors: Mashimo, Masato, Okubo, Yohei, Yamazawa, Toshiko, Yamasaki, Miwako, Watanabe, Masahiko, Murayama, Toshihiko, Iino, Masamitsu
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.11.2010
• Subjects: 5-trisphosphate; Amino Acid Transport System X-AG - metabolism; Animals; Astrocytes; Bergmann glia; Brain; calcium; Calcium - metabolism; Cerebellum; Cerebellum - cytology; Glia; Glial cells; glutamate/aspartate transporter (GLAST); Glutamatergic transmission; Glutamic Acid - metabolism; Glutamic acid transporter; Information processing; inositol 1; Inositol 1,4,5-trisphosphate; Inositol 1,4,5-Trisphosphate - metabolism; Inositol Polyphosphate 5-Phosphatases; Mice; Mice, Inbred C57BL; mouse; Nervous system; Neuroglia - cytology; Neuroglia - metabolism; Patch-Clamp Techniques; Phosphoric Monoester Hydrolases - genetics; Phosphoric Monoester Hydrolases - metabolism; Purine P2 receptors; Second Messenger Systems - physiology; Synapses; Synapses - physiology
• ISSN: 0953-816X; 1460-9568
• DOI: 10.1111/j.1460-9568.2010.07452.x

The maintenance of synaptic functions is essential for neuronal information processing in the adult brain. Astrocytes express glutamate transporters that rapidly remove glutamate from the extracellular space and they play a critical role in the precise operation of glutamatergic transmission. However, how the glutamate clearance function of astrocytes is maintained remains elusive. Here, we describe a maintenance mechanism for the glutamate uptake capacity of Bergmann glial cells (BGs) in the cerebellum. When inositol 1,4,5‐trisphosphate (IP3) signaling was chronically and selectively inhibited in BGs in vivo, the retention time of glutamate around parallel fiber–Purkinje cell synapses was increased. Under these conditions, a decrease in the level of the glutamate/aspartate transporter (GLAST) in BGs was observed. The same effects were observed after chronic in vivo inhibition of purinergic P2 receptors in the cerebellar cortex. These results suggest that the IP3 signaling cascade is involved in regulating GLAST levels in BGs to maintain glutamate clearance in the mature cerebellum.