GABAergic control of neurite outgrowth and remodeling during development and adult neurogenesis: general rules and differences in diverse systems

Abstract

During development, Gamma-aminobutyric acidergic (GABAergic) neurons mature at early stages, long before excitatory neurons. Conversely, GABA reuptake transporters become operative later than glutamate transporters. GABA is therefore not removed efficiently from the extracellular domain and it can exert significant paracrine effects. Hence, GABA-mediated activity is a prominent source of overall neural activity in developing CNS networks, while neurons extend dendrites and axons, and establish synaptic connections. One of the unique features of GABAergic functional plasticity is that in early development, activation of GABAA receptors results in depolarizing (mainly excitatory) responses and Ca2+ influx. Although there is strong evidence from several areas of the CNS that GABA plays a significant role in neurite growth not only during development but also during adult neurogenesis, surprisingly little effort has been made into putting all these observations into a common framework in an attempt to understand the general rules that regulate these basic and evolutionary well-conserved processes. In this review, we discuss the current knowledge in this important field. In order to decipher common, universal features and highlight differences between systems throughout development, we compare findings about dendritic proliferation and remodeling in different areas of the nervous system and species, and we also review recent evidence for a role in axonal elongation. In addition to early developmental aspects, we also consider the GABAergic role in dendritic growth during adult neurogenesis, extending our discussion to the roles played by GABA during dendritic proliferation in early developing networks versus adult, well established networks.

Succinic Semialdehyde Dehydrogenase: Biochemical–Molecular–Clinical Disease Mechanisms, Redox Regulation, and Functional Significance

“…GABA levels in null mouse brain are consistently threefold increased above normal, very consistent with levels measured in cerebrospinal fluid of patients (69,70,72,90). While these increases are not comparable to that of GHB, during embryonic development, and most likely for the first 1-2 weeks of life, GABA is excitatory in the developing rodent brain, primarily at the GABA(A) receptor (82,173), and this hyperGABAergic state in the mouse model may be a contributory factor to the evolution of seizures.…”

Non-hyperpolarizing GABAB receptor activation regulates neuronal migration and neurite growth and specification by cAMP/LKB1

“…Despite some contrasting results by few previous studies, there is general agreement that GABA B R signalling affects axonal growth and modulates neuronal migration in vitro 9,10 . In particular, in line with our data, GABA B R antagonist delayed migration of excitatory neurons from the IZ to the CP 17 , and produced accumulation of tangentially migrating interneurons (associated with a shorter leading neuronal process) in the VZ/SVZ of organotypic cortical slices independently of Kir channels 15 .…”

“…Furthermore, abundant endogenous GABA present in neonatal tissue 1,2,6,7 activates GABA B Rs 8 . Despite the extensive literature on the importance of GABA A R during early development 1,2,6,7,9 , the role of GABA B R has been poorly investigated and data are controversial 10 . For example, a role of GABA B R in neuronal morphological maturation was described in some systems 9,11,12 , but not in others 13 , and only in vitro evidence indicated that GABA B R modulates migration of immature neurons [14][15][16][17] .…”

“…Despite the extensive literature on the importance of GABA A R during early development 1,2,6,7,9 , the role of GABA B R has been poorly investigated and data are controversial 10 . For example, a role of GABA B R in neuronal morphological maturation was described in some systems 9,11,12 , but not in others 13 , and only in vitro evidence indicated that GABA B R modulates migration of immature neurons [14][15][16][17] . Furthermore, these in vitro data are in contrast with observations in a number of mouse strains genetically modified for GABA B Rs, which present grossly normal brain and cell morphology [18][19][20][21][22][23][24][25][26] .…”

Non–cell-autonomous factor induces the transition from excitatory to inhibitory GABA signaling in retina independent of activity

“…muscimol | nicotinic acetylcholine receptor | retinal waves | calcium imaging | BDNF A lthough GABA is the principal inhibitory neurotransmitter in the mature CNS, it is a robust source of excitation during development that is important for many developmental processes (1)(2)(3)(4). The transition from excitatory to inhibitory action of GABA has been observed in a number of neural circuits and in many vertebrate species (5,6) and the primary mechanisms underlying the switch are fairly well understood (7)(8)(9)(10)(11); reviewed in refs.…”