The speeding of EPSC kinetics during maturation of a central synapse

Abstract

Several factors contribute to the shape of excitatory postsynaptic currents (EPSCs) in CNS neurons, among them the kinetics of presynaptic release, transmitter clearance, and the properties and distribution of postsynaptic receptors. The decays of AMPA receptor-mediated EPSCs at rat cerebellar mossy fibre-granule cell (MF-gc) synapses follow a bi-exponential time-course. The fast component dominates the decay, accounting for 84-94% of the peak amplitude. Here we show that both components of decay, and also the risetimes, became faster during postnatal maturation. At adult, but not immature, synapses, the risetimes and decays of evoked multiquantal EPSCs were similar to those of monoquantal miniature (m)EPSCs. The faster risetimes at mature synapses reflected increased synchrony of multivesicular release, whereas the faster decays appeared to reflect changes in the properties of postsynaptic receptors. Inhibition of glutamate uptake was without effect on evoked EPSCs at both ages. Furthermore, after slowing receptor desensitization with cyclothiazide, the EPSCs at mature synapses decayed as slowly as EPSCs at immature synapses, suggesting that faster glutamate clearance does not account for the developmental speeding of EPSC decay. Our results support previous conclusions that glutamate clearance and receptor deactivation are important determinants of the fast decay component at immature synapses. Desensitization becomes increasingly important during development and plays a major role in shaping EPSC decay at mature synapses.

Mechanisms Underlying Developmental Speeding in AMPA-EPSC Decay Time at the Calyx of Held

“…This is in agreement with what is reported at chick auditory synapses (Brenowitz and Trussell, 2001) but contrasts with the report at the cerebellar granule cell synapse, where desensitization becomes increasingly important in shaping EPSC decay as animals mature (Wall et al, 2002). This conclusion is supported by the finding that the slowing effect of CTZ on the EPSC decay decreased with development, whereas that on the AMPA patch currents remained constant throughout development.…”

“…Developmental switches of postsynaptic receptor subunits underlie speeding in the decay time of synaptic currents mediated by nicotinic acetylcholine receptors (Mishina et al, 1986), glycine receptors (Takahashi et al, 1992), GABA A receptors (Okada et al, 2000), and NMDA receptors (NMDARs) Takahashi et al, 1996). Like other synaptic currents, the decay time of AMPA-EPSCs at the calyx of Held becomes faster during postnatal development (Taschenberger and von Gersdorff, 2000;Futai et al, 2001;Iwasaki and Takahashi, 2001;Joshi and Wang, 2002;Wall et al, 2002;Yamashita et al, 2003). However, it is not known whether the switch of AMPA receptor (AMPAR) subunits underlies this developmental speeding.…”

Altered Neuron Excitability and Synaptic Plasticity in the Cerebellar Granular Layer of Juvenile Prion Protein Knock-Out Mice with Impaired Motor Control

“…Moreover, immature granule cells show slow EPSPs in association with slow NMDA currents (D'Angelo et al, 1993;Farrant et al, 1994;Rumbaugh and Vicini, 1999;Cathala et al, 2000;Rossi et al, 2002;Wall et al, 2002). In normal mice, the transition from immature to mature excitable patterns occurs soon after granule cell migrate from the external to internal granular layer and proceeds throughout postnatal weeks 1 and 2: in week 3, electrophysiological parameters are stabilized and immature slowspiking granule cells disappear [for mice, see Rossi et al (1998); for the rat, see D'Angelo et al (1993D'Angelo et al ( , 1994D'Angelo et al ( , 1997].…”

The high variance of AMPA receptor- and NMDA receptor-mediated responses at single hippocampal synapses: Evidence for multiquantal release

“…There are many reasons to doubt that this requirement is met. These include (i) failures to stimulate the axon, (ii) all-or-none Ca 2ϩ signals in boutons (35), (iii) changes in Ca 2ϩ amplification in the terminal by internal release (36,37), and perhaps most importantly, (iv) stochastic variation in the number of Ca 2ϩ channels that open (4,38).…”

“…An important question relates to the number of vesicles that are released and the interaction between them. There are indications that transmission can be uniquantal at some synapses, but multiquantal at others (2)(3)(4).…”