Maturation of a Central Glutamatergic Synapse

Abstract

Whole-cell recordings from optic tectal neurons in Xenopus tadpoles were used to study the maturation of a glutamatergic synapse. The first glutamatergic transmission is mediated only by N-methyl-D-aspartate (NMDA) receptors and is silent at resting potentials. More mature synapses acquire transmission by alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors. This maturational program is mimicked by postsynaptic expression of constitutively active calcium-calmodulin-dependent protein kinase II (CaMKII). Newly formed synapses may be silent unless sufficient depolarization is provided by coincident activity that could activate postsynaptic CaMKII, resulting in the appearance of AMPA responses.

Retinocollicular Synapse Maturation and Plasticity Are Regulated by Correlated Retinal Waves

“…Additionally, this disappearance of silent synapses in many circuits coincides with the closure of the critical period for LTP induction (Crair and Malenka, 1995;Kirkwood et al, 1995), suggesting a mechanistic link. In direct support of this, experimental induction of LTP at putative silent synapses has been shown to convert NMDAR-only synapses into AMPAR-containing synapses, thereby rendering them functional at resting membrane potential (Liao et al, 1995;Durand et al, 1996;Wu et al, 1996;Isaac et al, 1997). Our results support such a model during the refinement of retinocollicular synapses, because correlated activity produces a developmental downregulation of silent synapses.…”

“…As relevant connections are made functional, therefore, there should be a concurrent developmental downregulation of silent synapses, and indeed such a profile has been observed in numerous brain regions (Isaac et al, 1995(Isaac et al, , 1997Wu et al, 1996;Rumpel et al, 1998;Franks and Isaacson, 2005). Additionally, this disappearance of silent synapses in many circuits coincides with the closure of the critical period for LTP induction (Crair and Malenka, 1995;Kirkwood et al, 1995), suggesting a mechanistic link.…”

“…This form of activity-dependent competition is thought to be mediated by NMDARs, because their dual ligand and voltage dependence allows for detection of coincident presynaptic and postsynaptic activity (Constantine-Paton and Cline, 1998;Zhang and Poo, 2001). In the frog retinotectal system, an NMDAR-dependent LTP-like process results in a developmental increase in AMPA/NMDA ratios at retinotectal synapses during map refinement (Wu et al, 1996). Interestingly, chronic NMDAR blockade serves to increase RGC arbor branch dynamics, suggesting that NMDAR activity and synaptic maturation normally stabilizes retinotectal projections during circuit formation (Rajan et al, 1999).…”

“…More mature synapses acquire transmission through AMPA receptors (AMPARs) over the course of normal development, and these effects can be hastened by experimentally inducing LTP (Liao et al, 1995;Durand et al, 1996;Wu et al, 1996;Isaac et al, 1997). NMDAR-dependent LTP is also observed during developmental periods in which activity can significantly affect patterns of structural connectivity (Crair and Malenka, 1995;Kirkwood et al, 1996), suggesting that activitydependent increases in synaptic strength may contribute to the stabilization of synaptic connections.…”

In VitroSynaptogenesis between the Somata of IdentifiedLymnaeaNeurons Requires Protein Synthesis But Not Extrinsic Growth Factors or Substrate Adhesion Molecules

“…Neither CM nor any exogenous substrate was required for synapse formation. In summary, our data provide direct evidence that synaptogenesis in this system requires specific, cell contact-induced, de novo protein synthesis but does not depend on extrinsic growth factors or substrate adhesion molecules.Key words: synapse formation; in vitro; growth factors; Lymnaea; soma-soma synapses; mollusks To f unction properly, the adult brain relies heavily on neuronal connectivity patterns that are orchestrated during early embryonic development (McMahan, 1990;Nelson et al, 1990;Goodman and Shatz, 1993;Hall and Sanes, 1993; Jessel and Kandel, 1993;Goodman, 1994Goodman, , 1996Grantyn et al, 1995;Katz and Shatz, 1996;Wu et al, 1996;Spencer et al, 1997). Yet, the cellular and molecular mechanisms (intrinsic and /or extrinsic) that determine the specificity of synaptic connections in the nervous system remain poorly understood.…”