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Depolarization promotes GAD 65‐mediated GABA synthesis by a post‐translational mechanism in neural stem cell‐derived neurons
Author(s) -
GakharKoppole Nidhi,
Bengtson C. Peter,
Parlato Rosanna,
Horsch Kerstin,
Eckstein Volker,
Ciccolini Francesca
Publication year - 2008
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2007.06020.x
Subject(s) - depolarization , neuroscience , glutamate decarboxylase , biology , microbiology and biotechnology , subventricular zone , glutamate receptor , neurogenesis , chemistry , neural stem cell , biophysics , biochemistry , receptor , stem cell , enzyme
Neuronal activity regulates neurogenesis and neuronal differentiation in the mammalian brain. The commencement of neurotransmitter expression establishes the neuronal phenotype and enables the formation of functional connectivity between neurons. In addition, release of neurotransmitters from differentiating neurons may modulate the behaviour of neural precursors. Here, we show that neuronal activity regulates γ‐aminobutyric acid (GABA) expression in neurons generated from stem cells of the striatum and adult subventricular zone (SVZ). Differentiating neurons display spontaneous Ca 2+ events, which are voltage‐gated calcium channel (VGCC) dependent. Depolarization increases both the frequency of Ca 2+ transients and the amount of Ca 2+ influx in differentiating neurons. We show that depolarization‐dependent GABA expression is regulated by the amplitude and not by the frequency of Ca 2+ influx. Brief activation of VGCCs leads to Ca 2+ influx that in turn promotes a rapid expression of GABA. Depolarization‐dependent GABA expression does not require changes in gene expression. Instead, it involves cAMP‐dependent protein kinase (PKA) and Ca 2+ and phospholipid‐dependent protein kinase (PKC) signalling. Activity increases the number of glutamic acid decarboxylase (GAD) 65‐immunoreactive neurons in a PKA‐dependent manner, without altering the expression of GAD 65, suggesting that depolarization promotes recruitment of GAD 65 by a post‐translational mechanism. In line with this, depolarization does not permanently increase the expression of GABA in neurons derived from neural stem cells of the embryonic striatum, cortex and adult SVZ. Thus, neuronal activity does not merely accelerate neuronal differentiation but it may alter the mechanism of GABA synthesis in newly generated neurons.