Abstract
Within the early period of mammalian ontogenic development, activation of GABAA receptors evokes in the central nervous system depolarization of the cellular membranes, instead of inhibition. In this review, we describe phenomenology and mechanisms underlying the effects related to this peculiarity, in particular a GABA-activated increase in the intracellular calcium concentration and oscillations of the latter in the hippocampal neuronal network. The physiological role of the GABA-mediated depolarizing synaptic activity (as a possible factor influencing formation of a glutamatergic synaptic network) is discussed.
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L. Sivilotti and A. Nistri, “GABA receptor mechanisms in the central nervous system,”Prog. Neurobiol.,36, 35–92 (1991).
D. A. Prince and B. W. Connors, “Mecanisms of interictal epileptogenesis,”Adv. Neurol.,44, 275–299 (1986).
Y. Ben-Ari, E. Cherubini, R. Corradetti, and J. L. Gaiarsa, “Giant synaptic potentials in immature rat CA3 hippocampal neurones.J. Physiol.,416, 303–325 (1989).
R. Yuste and L. C. Katz, “Control of postsynaptic Ca2+ influx in developing neocortex by excitatory and inhibitory neurotransmitters,”Neuron,6, 333–344 (1991).
D. B. Reichling, A. Kyrozis, J. Wang and A. B. MacDermott, “Mechanisms of GABA and glycine depolarization-induced calcium transients in rat dorsal horn neurons,”J. Physiol.,476, 411–421 (1994).
G. Chen, P. Q. Tromble, and A. N. van den Pol, “Excitatory actions of GABA in developing rat hypothalamic neurones,”J. Physiol.,494, 451–464 (1996).
R. Serafini, A. Y. Valeyev, J. L. Barker, and M. O. Poulter, “Depolarizing GABA-activated Cl− channels in embryonic rat spinal and olfactory bulb cells,”J. Physiol.,488, 371–386 (1995).
D. F. Owens, L. H. Boyce, M. B. Davis, and A. R. Kriegstein, “Excitatory GABA responses in embryonic and neonatal cortical slices demonstrated by gramicidin perforated-patch recordings and calcium imaging,”J. Neurosci.,16, 6414–6423 (1996).
O. Garaschuk, E. Hanse, and A. Konnerth, “Developmental profile and synaptic origin of early network oscillations in theCA1 region of rat neonatal hippocampus,”J. Physiol.,507, 219–236 (1998).
M. H. Lin, M. P. Takahashi, Y. Takahashi, and T. Tsumoto, “Intracellular calcium increase induced by GABA in visual cortex of fetal and neonatal rats and its disappearance with development,”Neurosci. Res.,20, 85–94 (1994).
X. Leinekugel, I. Medina, I. Khalilov, et al., “Ca2+ oscillations mediated by the synergistic excitatory action of GABAA and NMDA receptors in the neonatal hippocampus,”Neuron,18, 243–255 (1997).
K. Obrietan, and A. N. van den Pol, “GABA neurotransmission in the hypothalamus: developmental reversal from Ca2+ elevating to depressing,”J. Neurosci.,15, 5065–5077 (1995).
X. Leinekugel, V. Tseeb, Y. Ben-Ari, and P. Bregestovski, “Synaptic GABAA activation induces Ca2+ rise in pyramidal cells and interneurons from rat neonatal hippocampal slices,”J. Physiol.,487, 315–321 (1995).
B. Huang, and D. A. Redburn, “GABA-induced increases in [Ca2+] i in retinal neurons of postnatal rabbits,”Vis. Neurosci.,13, 441–447 (1996).
O. Garaschuk, E. Hanse, and A. Konnerth, “Mechanisms underlying oscillatory Ca2+ waves in the developing hippocampus,”Eur. J. Physiol.,433 Suppl., R-31 (1997).
D. Janigro, and P. A. Schwartzkroin, “Effects of GABA and baclofen on pyramidal cells in the developing rabbit hippocampus: anin vitro study,”Brain Res.,469, 171–184 (1988).
J. Rohrbough, and N. C. Spitzer, “Regulation of intracellular CT levels by Na+-dependent Cl− cotransport distinguishes depolarizing from hyperpolarizing GABAA receptor-mediated responses in spinal neurons,”J. Neurosci.,16, 82–91 (1996).
J. J. LoTurco, D. F. Owens, M. J. S. Heath, et al., “GABA and glutamate depolarize cortical progenitor cells and inhibit DNA synthesis,”Neuron,15, 1287–1298 (1995).
K. Staley, R. Smith, J. Schaack, et al., “Alteration of GABAA receptor function following gene transfer of the CLC-2 chloride channel,”Neuron,17, 543–51 (1996).
G. M. Durand, Y. Kovalchuk, and A. Konnerth, “Long-term potentiation and functional synapse induction in developing hippocampus,”Nature,381, 71–75 (1996).
Y. Hosokawa, M. Sciancalepore, F. Stratta, et al., “Developmental changes in spontaneous GABAA-mediated synaptic events in rat hippocampalCA3 neurons,”Eur. J. Neurosci.,6, 805–813 (1994).
D. Liao, and R. Malinow, “Deficiency in induction but not expression of LTP in hippocampal slices from young rats,”Learning Memory,3, 138–149 (1996).
T. V. Dunwiddie, “Age-related differences in thein vitro rat hippocampus. Development of inhibition and the effects of hypoxia”,Dev. Neurosci.,4, 165–175 (1994).
K. M. Harris and T. J. Teyler, “Evidence for late development of inhibition in areaCA1 of the rat hippocampus”,Brain Res.,268, 339–343 (1983).
J. W. Swann, R. J. Brady and D. L. Martin, “Postnatal development of GABA-mediated synaptic inhibition in rat hippocampus”,Neuroscience,28, 551–561 (1989).
R. Khazipov, X. Leinekugel, I. Khalilov, et al., “Synchronization of GABAergic interneuronal network inCA3 subfield of neonatal rat hippocampal slices”,J. Physiol. 498, 763–772 (1997).
E. Cherubini, J. L. Gaiarsa, and Y. Ben Ari, “GABA: an excitatory transmitter in early postnatal life”,Trends Neurosci.,14, 515–519 (1991).
E. Hanse, G. M. Durand, O. Garaschuk, and A. Konnerth, “Activity-dependent wiring of the developing hippocampal neuronal circuit”,Semin. Cell Dev. Biol.,8, 35–42 (1997).
Y. Ben-Ari, R. Khazipov, X. Leinekugel, et al., “GABAA, NMDA, and AMPA receptors: a developmentally regulated ‘menage a trois”,Trends Neurosci.,20, 523–529 (1997).
J. M. Lauder, V. K. Han, P. Henderson, et al., “Prenatal ontogeny of the GABAergic system in the rat brain: an immunocytochemical study.Neuroscience,19, 465–493 (1986).
P. E. Spoerri, “Neurotrophic effects of GABA in cultures of embryonic chick brain and retina”,Synapse,2, 11–22 (1988).
Y. Ben-Ari, V. Tseeb, D. Raggozzino, et al., “γ-Aminobutyric acid (GABA): a fast excitatory transmitter which may regulate the development of hippocampal neurons in early postnatal life”,Prog. Brain Res.,102, 261–273 (1994).
T. N. Behar et al., “GABA stimulates chemotaxis and chemokinesis of embryonic cortical neurons via calcium-dependent mechanisms,”J. Neurosci.,16, 1808–1818 (1996).
S. Marty, B. Beminger, P. Carroll, and H. Thoenen, “GABAergic stimulation regulates the phenotype of hippocampal interneurons through the regulation of brain-derived neurotrophic factor,”Neuron,16, 565–570 (1996).
H. Bading, D. D. Ginty, and M. E. Greenberg, “Regulation of gene expression in hippocampal neurons by distinct calcium signaling pathways”,Science,260, 181–186 (1993).
A. Ghosh, D. D. Ginty, H. Bading, and M. E. Greenberg, “Calcium regulation of gene expression in neuronal cells”,J. Neurobiol.,25, 294–303 (1994).
A. Ghosh and M. E. Greenberg, “Calcium signaling in neurons: molecular mechanisms and cellular consequences”,Science,268, 239–247 (1995).
N. C. Spitzer, “Spontaneous Ca2+ spikes and waves in embryonic neurons: signaling systems for differentiation”,Trends Neurosci.,17, 115–118 (1994).
J. L. Franklin and E. M. Jr. Johnson, “Suppression of programmed neuronal death by sustained elevation of cytoplasmic calcium”,Trends Neurosci.,15, 501–508 (1992).
G. Rusanescu, H., Qi, S. M. Thomas, et al., “Calcium influx induces neurite growth through a Src-Ras signaling cassette”,Neuron,15, 1415–1425 (1995).
S. B. Kater, M. P. Mattson, C. Cohan, and J. Connor, “Calcium regulation of the neuronal growth cone”,Trends Neurosci.,11, 315–321 (1988).
S. B. Kater and S. A. Lipton, “Neurotransmitter regulation of neuronal outgrowth, plasticity and survival in the year 2001”,Trends Neurosci.,18, 71–72 (1995).
K. M. Harris and T. J. Teyler, “Developmental onset of long-term potentiation in areaCA1 of the rat hippocampus”,J. Physiol. 346, 27–48 (1984).
D. Muller, M. Oliver, and G. Lynch, “Developmental changes in synaptic properties in hippocampus of neonatal rats”,Dev. Brain Res.,49, 105–114 (1989).
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Garaschuk, O.V. Depolarizing action of GABA on neurons of the central nervous system during early postnatal development. Neurophysiology 31, 258–262 (1999). https://doi.org/10.1007/BF02515099
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DOI: https://doi.org/10.1007/BF02515099