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 ␥-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. mossy fibers ͉ synaptic plasticity ͉ GABA-mediated oscillatory events ͉ development ͉ synaptic pairing

In the adult rat hippocampus, granule cell mossy fibers (MFs) form excitatory glutamatergic synapses with CA3 principal cells and local inhibitory interneurons. However, evidence has been provided that, in young animals and after seizures, the same fibers can release in addition to glutamate GABA. Here we show that, during the first postnatal week, stimulation of granule cells in the dentate gyrus gave rise to monosynaptic GABA A -mediated responses in principal cells and in interneurons. These synapses were indeed made by MFs because they exhibited strong paired-pulse facilitation, high sensitivity to the metabotropic glutamate receptor agonist L-AP-4, and short-term frequency-dependent facilitation.

Glutamate transporters are responsible for clearing synaptically released glutamate from the extracellular space. By this action, they maintain low levels of ambient glutamate, thus preventing excitotoxic damage, and contribute to shaping synaptic currents. We show that up-regulation of the glutamate transporter GLT-1 by ceftriaxone severely impaired mGluR-dependent long-term depression (LTD), induced at rat mossy fibre (MF)-CA3 synapses by repetitive stimulation of afferent fibres. This effect involved GLT-1, since LTD was rescued by the selective GLT-1 antagonist dihydrokainate (DHK). DHK per se produced a modest decrease in fEPSP amplitude that rapidly regained control levels after DHK wash out. Moreover, the degree of fEPSP inhibition induced by the low-affinity glutamate receptor antagonist γ-DGG was similar during basal synaptic transmission but not during LTD, indicating that in ceftriaxone-treated rats LTD induction did not alter synaptic glutamate transient concentration. Furthermore, ceftriaxone-induced GLT-1 up-regulation significantly reduced the magnitude of LTP at MF-CA3 synapses but not at Schaffer collateral-CA1 synapses. Postembedding immunogold studies in rats showed an increased density of gold particles coding for GLT-1a in astrocytic processes and in mossy fibre terminals; in the latter, gold particles were located near and within the active zones. In both CEF-treated and untreated GLT-1 KO mice used for verifying the specificity of immunostaining, the density of gold particles in MF terminals was comparable to background levels. The enhanced expression of GLT-1 at release sites may prevent activation of presynaptic receptors, thus revealing a novel mechanism by which GLT-1 regulates synaptic plasticity in the hippocampus.