GABA Depolarizes Neuronal Progenitors of the Postnatal Subventricular Zone Via GABAA Receptor Activation

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Abstract
Previous studies have reported the presence of migrating and dividing neuronal progenitors in the subventricular zone (SVZ) and rostral migratory stream (RMS) of the postnatal mammalian brain. Although the behaviour of these progenitors is thought to be influenced by local signals, the nature and mode of action of the local signals are largely unknown. One of the signalling molecules known to affect the behaviour of embryonic neurons is the neurotransmitter GABA. In order to determine whether GABA affects neuronal progenitors via the activation of specific receptors, we performed cell-attached, whole-cell and gramicidin perforated patch-clamp recordings of progenitors in postnatal mouse brain slices containing either the SVZ or the RMS. Recorded cells displayed a morphology typical of migrating neuronal progenitors had depolarized zero-current resting potentials, and lacked action potentials. A subset of progenitors contained GABA and stained positive for glutamic acid decarboxylase 67 (GAD-67) as shown by immunohistochemistry. In addition, every neuronal progenitor responded to GABA via picrotoxin-sensitive GABAA receptor (GABAAR) activation. GABAARs displayed an ATP-dependent rundown and a low sensitivity to Zn2+. GABA responses were sensitive to benzodiazepine agonists, an inverse agonist, as well as a barbiturate agonist. While GABA was hyperpolarizing at the zero-current resting potentials, it was depolarizing at the cell resting potentials estimated from the reversal potential of K+ currents through a cell-attached patch. Thus, our study demonstrates that neuronal progenitors of the SVZ/RMS contain GABA and are depolarized by GABA, which may constitute the basis for a paracrine signal among neuronal progenitors to dynamically regulate their proliferation and/or migration.