Spontaneous unitary synaptic activity in CA1 pyramidal neurons during early postnatal development: Constant contribution of AMPA and NMDA receptors

University of Gothenburg, Goeteborg, Västra Götaland, Sweden
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience (Impact Factor: 6.34). 08/2002; 22(13):5552-62.
Source: PubMed


Maturation of the glutamatergic synapse is thought to require the incorporation of AMPA receptors at pure NMDA synapses, also called "silent" synapses. However, the relative number of silent synapses at different developmental stages, and even the concept that silent synapses lack AMPA receptors, is actively debated. In the present work, spontaneous synaptic events were used to investigate the relative contribution of synaptic AMPA and NMDA receptor-mediated transmission in CA1 pyramidal cells during the early postnatal development. Spontaneous postsynaptic currents, mediated by AMPA and NMDA receptors, were recorded from visualized CA1 pyramidal neurons over the first postnatal week. AMPA/NMDA ratio for frequency was close to one, and, importantly, it was constant over the first postnatal week. These findings suggest that the vast majority of nascent glutamatergic synapses express both functional AMPA and NMDA receptors in the neonatal hippocampus.

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    • "AMPAR EPSC amplitude was measured as the mean amplitude during a 2 ms window around the negative peak. NMDAR EPSC amplitude was recorded in voltage-clamp at +40 mV and measured as the mean positive amplitude between 50–60 ms after onset [28]. fEPSP size was estimated using a linear regression of the 0.8 ms initial slope. "
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    ABSTRACT: Agonist-induced internalization of transmembrane receptors is a widespread biological phenomenon that also may serve as a mechanism for synaptic plasticity. Here we show that the agonist AMPA causes a depression of AMPA receptor (AMPAR) signaling at glutamate synapses in the CA1 region of the hippocampus in slices from developing, but not from mature, rats. This developmentally restricted agonist-induced synaptic depression is expressed as a total loss of AMPAR signaling, without affecting NMDA receptor (NMDAR) signaling, in a large proportion of the developing synapses, thus creating AMPAR silent synapses. The AMPA-induced AMPAR silencing is induced independently of activation of mGluRs and NMDARs, and it mimics and occludes stimulus-induced depression, suggesting that this latter form of synaptic plasticity is expressed as agonist-induced removal of AMPARs. Induction of long-term potentiation (LTP) rendered the developing synapses resistant to the AMPA-induced depression, indicating that LTP contributes to the maturation-related increased stability of these synapses. Our study shows that agonist binding to AMPARs is a sufficient triggering stimulus for the creation of AMPAR silent synapses at developing glutamate synapses.
    Full-text · Article · Apr 2012 · PLoS ONE
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    • "On the other hand, there is electrophysiological evidence indicating that, at least under conditions of high release probability, GABA synapses [24] and glutamate synapses [25-27] onto mature CA1 pyramidal cells are capable of multivesicular release. In contrast to these findings in mature CA3-CA1 glutamate synapses, electrophysiological studies of developing (during the first two postnatal weeks in the rodent) CA3-CA1 synapses have shown that these connections have univesicular release [4,8,15,28]. For glutamate synapses the issue of multi- versus univesicular release is complicated by whether AMPA or NMDA receptors are used as reporters in electrophysiological studies [27]. "
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    • "sIPSCs at the reversal potential of sEPSCs (+10 mV). To record sEPSCs we continuously applied a GABA A receptor antagonist (bicuculline 20 μM or Gabazine 5 μM), and maintained the membrane potential at −80 or +40 mV to separately detect AMPA/kainate (KA) and NMDA sEPSCs, respectively (Groc et al., 2002). We recorded AMPA/KA sEPSCs in the continuous presence of APV (40 μM), the selective NMDA receptor antagonist, and separated AMPA from KA sEPSCs by applying NBQX at a dose (1 μM) that preferentially blocks AMPA receptors. "
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