GABA excites immature CA3 pyramidal cells through bicuculline-sensitive and -insensitive chloride-dependent receptors

E. Cherubini*, M. Martina, M. Sciancalepore, F. Strata

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

20 Scopus citations

Abstract

Intracellular and patch clamp recording techniques were used to investigate the role of GABA in immature CA3 hippocampal neurons. During the first postnatal week spontaneous GABA release was detected as spontaneous ongoing synaptic potentials (SPSPs) or giant depolarizing potentials (GDPs). GDPs were generated at regular intervals and regulated by ionotropic glutamate receptors (GluRs), whereas SPSPs occurred randomly and were unaffected by ionotropic GluRs. Both GDPs and SPSPs were positively modulated by metabotropic GluRs through cyclic AMP-dependent protein kinase. Moreover GABA controlled its own release through GABA(A) and GABA(B) receptors, probably localized on GABAergic nerve terminals. At this developmental stage, GABA depolarized CA3 pyramidal cells through two distinct classes of chloride-permeable receptors: bicuculline sensitive and insensitive, respectively. The bicuculline-insensitive responses were blocked by picrotoxin in a noncompetitive way. Whole-cell GABA currents, recorded in the presence of bicuculline, had a slower desensitization rate and faster recovery from desensitization. In excised outside-out patches, in the presence of bicuculline, GABA activated single-channel currents with conductances of 14, 22, and 31 pS. These values were similar to those obtained when GABA was applied in the absence of bicuculline. Interestingly, GABA responses obtained in the absence of bicuculline, were sensitive to the blocking effect of zinc, whereas bicuculline-resistant responses were almost unaffected by this divalent cation. Expression of different subunits in native receptors (particularly of the α and ρ type) may account for the functional differences observed in the present experiments. Activation of bicuculline-insensitive receptors would strengthen and prolong the depolarizing action of GABA, thus favoring the entry of calcium through voltage-dependent calcium channels. This calcium signal may be essential in promoting stabilization of synaptic contacts during a critical period of postnatal development.

Original languageEnglish (US)
Pages (from-to)289-304
Number of pages16
JournalPerspectives on Developmental Neurobiology
Volume5
Issue number2-3
StatePublished - Nov 17 1998

Keywords

  • γ-Aminobutyric Acid
  • Baclofen-Insensitive Receptors
  • Bicuculline-
  • CA3 Region
  • Development
  • Giant Depolarizing Potentials (GDPs)
  • Hippocampus
  • Spontaneous Postsynaptic Potentials (SPSPs)

ASJC Scopus subject areas

  • Neuroscience(all)
  • Developmental Biology

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