A Developmental Switch in Neurotransmitter Flux Enhances Synaptic Efficacy by Affecting AMPA Receptor Activation

Abstract

Formation of glutamatergic synapses entails development of "silent" immature contacts into mature functional synapses. To determine how this transformation occurs, we investigated the development of neurotransmission at single synapses in vitro. Maturation of presynaptic function, assayed with endocytotic markers, followed accumulation of synapsin I. During this period, synaptic transmission was primarily mediated by activation of NMDA receptors, suggesting that most synapses were functionally silent. However, local glutamate application to silent synapses indicated that these synapses contained functional AMPA receptors, suggesting a possible presynaptic locus for silent transmission. Interference with presynaptic vesicle fusion by exposure to tetanus toxin reverted functional to silent transmission, implicating SNARE-mediated fusion as a determinant of the ratio of NMDA:AMPA receptor activation. This work reveals that functional maturation of synaptic transmission involves transformation of presynaptic silent secretion into mature synaptic transmitter release.

Ontogeny of postsynaptic density proteins at glutamatergic synapses

“…However, if those from 2 animals showed a significant difference, then a third animal was included in the count. Immunogold labeling was not counted per unit length of the synapse, because we found in our previous study that the values of gold per synapse versus gold per micrometer length of the synapse were similar for these ages ; lack of significant change of synapse length during development is noted also for hippocampal neurons in vitro by Renger et al [2001] and reviewed in general by Ziv and Garner [2004]). Thus, the gold per synapse values given here can be compared readily with those already published using the same method Sans et al, 2000); this is the most efficient method of comparing results among proteins found in the same region and during the same developmental sequence.…”

The diversity of subunit composition in nAChRs: Evolutionary origins, physiologic and pharmacologic consequences

“…Interestingly, the bacterial networks exhibit a topology similar to the network proposed by Kneussel and Betz (2000) for the clusters of GABA and glycine receptors. Furthermore, the receptors are not frozen in this complex environment and their distribution patterns can be modified by activity (Renger et al, 2000). Neurotransmitter receptors can move across the plasma membrane, and aggregate (Meier et al, 2001;Sergé et al, 2002), and even can be transferred back and forth to an intracellular pool (Barry and Ziff, 2002).…”

Active zones for presynaptic plasticity in the brain

“…It has been proposed that a similar mechanism might underlie the conversion of immature silent synapses into mature functional synaptic contacts. 56 Although Choi et al 55 favored the fusion pore explanation, they did not rule out that the slow-rising EPSCs could be generated instead by spillover from neighbor synapses rather than from a slow releasing fusion pore. Recently, Nielsen et al 57 have reported that at cerebellar mossy fiber-granule cell synapses glutamate spillover from other synapses is the main cause for slow-rising EPSCs.…”