γ-Aminobutyric acid (GABA): A fast excitatory transmitter which may regulate the development of hippocampal neurons in early postnatal life

Y. Ben-Ari, V. Tseeb, D. Raggozzino, R. Khazipov, J. L. Gaiarsa

Research output: Contribution to journalArticle

Abstract

The properties of neonatal GABAergic synapses were investigated in neurones of the hippocampal CA3 region. GABA, acting on GABA(A) receptors, provides most of the excitatory drive on immature CA3 pyramidal neurones at an early stage of development, whereas glutamatergic synapses (in particular, those mediated by AMPA receptors) are mostly quiescent. Thus, during the first postnatal week of life, bicuculline fully blocked spontaneous and evoked depolarising potentials, and GABA(A) receptor agonists depolarised CA3 pyramidal neurones. GABA(A) mediated currents also had a reduced sensitivity to benzodiazepines. In the presence of bicuculline, between P0 and P4, increasing the stimulus strength reveals an excitatory postsynaptic potential which is mostly mediated by NMDA receptors. During the same developmental period, pre- (but not post) synaptic GABA(B) inhibition is present. Intracellular injections of biocytin showed that the axonal network of the GABAergic interneurones is well developed at birth, whereas the pyramidal recurrent collaterals are only beginning to develop. Finally, chronic bicuculline treatment of hippocampal neurones in culture reduced the extent of neuritic arborisation, suggesting that GABA acts as a trophic factor in that period. In conclusion, it is suggested that during the first postnatal week of life, when excitatory inputs are still poorly developed, GABA(A) receptors provide the excitatory drive necessary for pyramidal cell outgrowth. Starting from the end of the first postnatal week of life, when excitatory inputs are well developed, GABA (acting on both GABA(A) and GABA(B) receptors) will hyperpolarise the CA3 pyramidal neurones and, as in the adult, will prevent excessive neuronal discharges. Our electrophysiological and morphological studies have shown that hippocampal GABAergic interneurones are in a unique position to modulate the development of CA3 pyramidal neurones. Developing neurones require a certain degree of membrane depolarisation, and a consequent rise in intracellular calcium, for stimulating neurite outgrowth; the GABAergic network, which develops prior to the glutamatergic one, appears to provide this depolarisation. Starting from the end of the first postnatal week of life, at a time when excitatory pathways are developing, GABA (acting on both GABA(A) and GABA(B) receptors) would reverse its action, and start to play its well-known role as an inhibitory neurotransmitter.

Original languageEnglish
Pages (from-to)261-273
Number of pages13
JournalProgress in Brain Research
Volume102
Publication statusPublished - 1994

ASJC Scopus subject areas

  • Neuroscience(all)

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