GABA-mediated giant depolarizing potentials as coincidence detectors for enhancing synaptic efficacy in the developing hippocampus

  1. Alexander M. Kasyanov*,
  2. Victoria F. Safiulina*,,
  3. Leon L. Voronin, and
  4. Enrico Cherubini*,
  1. *Neuroscience Programme, International School for Advanced Studies, 34014 Trieste, Italy; and Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Butlerova 5a, 117485 Moscow, Russia
  1. Edited by Per O. Andersen, University of Oslo, Oslo, Norway, and approved January 14, 2004 (received for review September 16, 2003)

Abstract

Spontaneously occurring neuronal oscillations constitute a hallmark of developmental networks. They have been observed in the retina, neocortex, hippocampus, thalamus, and spinal cord. In the immature hippocampus, the so-called “giant depolarizing potentials” (GDPs) are network-driven synaptic events generated by γ-aminobutyric acid (GABA), which at this stage is depolarizing and excitatory. We have tested the hypothesis that during the first postnatal week, GDP-associated calcium signals may alter the properties of synaptic transmission at poorly developed mossy fiber (MF)-CA3 connections. We found that “pairing” GDPs with MF stimulation induced a persistent increase in synaptic efficacy at MF-CA3 synapses. When the interval between GDPs and MF stimulation was increased, the potentiating effect progressively declined and disappeared. The potentiation depended on activation of voltage-dependent calcium channels and calcium flux. This activity may contribute to the refinement of neuronal connectivity before the establishment of the adult neuronal circuit.

Footnotes

  • To whom correspondence should be addressed. E-mail: cher{at}sissa.it.

  • This paper was submitted directly (Track II) to the PNAS office.

  • Abbreviations: GABA, γ-aminobutyric acid; CPP, α-3-(2-carboxy-piperazin-4-yl)-propyl-1-phosphonic acid; CV, coefficient of variation; d-AP5, d-(-)-2-amino-5-phosphonopentanoic acid; DCG-IV, (2S,2′R,3′R)-2-2(2′,3′-dicarboxycyclopropyl) glycine; EPSC, excitatory postsynaptic current; GDPs, giant depolarizing potentials; lAP-4, 2-amino-4-phosphonobutyric acid; LTP, long-term potentiation; MF, mossy fibers; NMDA, N-methyl-d-aspartate; VDCC, voltage-dependent calcium channels; DG, dentate gyrus; BAPTA, 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid; Pn, postnatal day n.

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