Abstract
Cortical computations rely on functionally diverse and highly dynamic synapses. How their structural composition affects synaptic transmission and plasticity and whether they support functional diversity remains rather unclear. Here, synaptic boutons on layer 5B (L5B) pyramidal neurons in the adult rat barrel cortex were investigated. Simultaneous patch-clamp recordings from synaptically connected L5B pyramidal neurons revealed great heterogeneity in amplitudes, coefficients of variation (CVs), and failures (F%) of EPSPs. Quantal analysis indicated multivesicular release as a likely source of this variability. Trains of EPSPs decayed with fast and slow time constants, presumably representing release from small readily releasable (RRP; 5.40 ± 1.24 synaptic vesicles) and large recycling (RP; 74 ± 21 synaptic vesicles) pools that were independent and highly variable at individual synaptic contacts (RRP range 1.2–12.8 synaptic vesicles; RP range 3.4–204 synaptic vesicles). Most presynaptic boutons (~85%) had a single, often perforated active zone (AZ) with a ~2 to 5-fold larger pre- (0.29 ± 0.19 μm2) and postsynaptic density (0.31 ± 0.21 μm2) when compared with even larger CNS synaptic boutons. They contained 200–3400 vesicles (mean ~800). At the AZ, ~4 and ~12 vesicles were located within a perimeter of 10 and 20 nm, reflecting docked and readily releasable vesicles of a putative RRP. Vesicles (~160) at 60–200 nm constituting the structural estimate of the presumed RP were ~2-fold larger than our functional estimate of the RP although both with a high variability. The remaining constituted a presumed large resting pool. Multivariate analysis revealed two clusters of L5B synaptic boutons distinguished by the size of their resting pool. Our functional and ultrastructural analyses closely link stationary properties, temporal dynamics and endurance of synaptic transmission to vesicular content and distribution within the presynaptic boutons suggesting that functional diversity of L5B synapses is enhanced by their structural heterogeneity.
Highlights
Synapses between different neurons in the brain are tuned to support computations specific to the neural networks in which they are embedded
Means ± SDs are given for individual animals
Our comprehensive functional and structural analysis of L5B excitatory synapses indicate simultaneous release of multiple synaptic vesicles from the functionally defined RRP that corresponds to a small pool of docked and short distance vesicles (p10 and p20 nm from the PreAZ)
Summary
Synapses between different neurons in the brain are tuned to support computations specific to the neural networks in which they are embedded. Several comprehensive studies have described structure-function relationships in peripheral (Dawson-Scully et al, 2007; Ehmann et al, 2014; reviewed by Denker et al, 2009), sensory (reviewed by Wichmann and Moser, 2015), brain stem (Rowland et al, 2000; Sätzler et al, 2002; reviewed by Borst and van Hoeve, 2012) and hippocampal (Harris and Sultan, 1995; Schikorski and Stevens, 1997; Rollenhagen et al, 2007; Branco et al, 2010; reviewed by Bischofberger et al, 2006; Rollenhagen and Lübke, 2010; Harris and Weinberg, 2012), and cerebellar synapses (Xu-Friedman et al, 2001; Xu-Friedman and Regehr, 2003) These studies demonstrated that structural subelements, in particular the number, size and organization of active zones (AZs) and that of the pools of synaptic vesicles play a pivotal role in synaptic transmission, but are organized in unique ways to foster functional specializations. Whether a resting pool exists in all synapses and under which conditions it might be utilized, remains unresolved
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