Seminar : 'Astrocytic GABA: biosynthesis, release, and function.' by Prof. Changjoon Justin Lee

Speaker : Prof. Changjoon Justin Lee, KIST (Korea Institute of Science and Technology)

http://glia.kist.re.kr/english/viewtopic.php?t=338&sid=731d89dab7373b5ac510e8fc6aca8559

Title: Astrocytic GABA: biosynthesis, release, and function.

Abstract:

Tonic inhibition has a critical role in brain functions under physiological and pathological conditions by controlling excitation/inhibition balance through modulating the neuronal excitability. Many studies have focused on manipulating the extrasynaptic GABAA receptors (GABAAR), the molecular target for the tonically released GABA to investigate the functional role of tonic inhibition in the brain. However, due to the variety of GABAAR subunits consisting of 16 subunits and the pentameric composition plus each subunit’s differential regional expression pattern, it has been extremely difficult to study the in vivo function of the tonic inhibition. Through a series of previous papers, we have demonstrated that the cerebellar tonic inhibition is mediated by the astrocytic GABA, synthesized by astrocyte-specific monoamine oxidase B (MAOB) enzyme and released via GABA-permeable Best1 channel. In the current study, using the pharmacological and genetic tools to manipulate astrocytic GABA, we demonstrate for the first time the in vivo function of cerebellar tonic inhibition. Our study clearly demonstrates that there is an inverse correlation between the level of astrocytic tonic GABA and motor performance. We further demonstrate that the astrocytic tonic GABA controls motor coordination by tonically inhibiting the cerebellar neuronal excitability. We believe that our findings will have profound implications in establishing the novel role of astrocytic GABA in excitation/inhibition balance in cerebellum and motor coordination as well as in depression, seizure, stress, schizophrenia, and autism. We anticipate that the pharmacological, molecular and genetic tools that we have characterized in this study will be widely utilized for studying such psychiatric disorders that may have disturbed excitation/inhibition balance.

Reference:

Soojung Lee, Bo Eun Yoon, Ken Berglund, Hyungju Park, Hee-Sup Shin, George J. Augustine, C. Justin Lee. Channel-mediated Tonic GABA Release from Glia.  Science. 2010 Nov 5;330(6005):790-6 (IF: 29.747)

Host: Prof. Erik De Schutter (Computational Neuroscience Unit)