The morphology of excitatory central synapses: from structure to function

Abstract

Synapses are the key elements for signal transduction and plasticity in the brain. For a better understanding of the functional signal cascades underlying synaptic transmission, a quantitative morphological analysis of the pre- and postsynaptic structures that represent morphological correlates for synaptic transmission is important. In particular, realistic values of the number, distribution, and geometry of synaptic contacts and the organization of the pool of synaptic vesicles provide important constraints for realistic models and numerical simulations of those parameters of synaptic transmission that, at present, are still not accessible to experiment. Although all synapses are composed of almost the same structural elements, the composition of these elements within a given synapse and the microcircuit in which they are embedded are the deciding factors determining its function. One possible way to analyze these structures is by computer-assisted three-dimensional reconstructions of synapses and their subsequent quantitative analysis based on ultrathin serial sections. The present review summarizes and discusses the morphology of five central excitatory synapses that are quantitatively well described: (1) a giant synapse, the so-called Calyx of Held, in the medial nucleus of the trapezoid body in the auditory brain stem, (2) the mossy fiber terminal establishing synapses with multiple cerebellar granule cell dendrites, (3) the mossy fiber bouton in the hippocampus predominantly terminating on proximal dendrites of CA3 pyramidal neurons, (4) the climbing fiber-Purkinje cell synapse in the cerebellum, and (5) cortical input synapses on the basal dendrites of layer 5 pyramidal cells. The detailed morphological description of these synaptic structures may help to define the morphological correlates of the functional parameters of synaptic transmission, such as the readily releasable pool of synaptic vesicles, of release, and of the variability of quantal size and might therefore explain the existing differences in the function between individual synapses embedded in different microcircuits.

Encoding and Decoding Bursts by NMDA Spikes in Basal Dendrites of Layer 5 Pyramidal Neurons

“…Recent work by Lefort et al (2009) has also revealed high-amplitude synaptic connections in all types of neurons in the somatosensory column producing EPSPs up to 7.8 mV, which are important in driving the network to fire. It is also the case that synaptic connections between cortical neurons can form clusters of two to five closely spaced synaptic contacts per site (Rollenhagen and Lübke, 2006). Based on these anatomical and physiological data, the presynaptic innervation pattern assumption of our model, in which relatively strong unitary connections are mapped to specific branches, is a reasonable description of an important subset of the presynaptic input to pyramidal neuron basal dendrites.…”

Quantitative ultrastructural analysis of basket and axo-axonic cell terminals in the mouse hippocampus

“…It was shown in several studies that morphological parameters of synaptic boutons (size and shape of boutons; number of postsynaptic targets; number, arrangement and size of active zones; number and size of mitochondria; presence of dense core vesicles etc.) can correlate well with their physiological properties (Kubota and Kawaguchi, 2000;Telgkamp et al, 2004;Rollenhagen and Lübke, 2006;Bodor et al, 2008;Yoshida et al, 2011;Holderith et al, 2012). After 3-dimensional reconstruction of perisomatic boutons, we measured these parameters to allow a comparison to their different functional properties and found that differences among interneuron types are manifested even in the finest ultrastructural details of their terminals possibly reflecting the adjustment of the signalling and vesicular release machinery to the requirements of the activity pattern.…”

Combined Optogenetic and Freeze-fracture Replica Immunolabeling to Examine Input-specific Arrangement of Glutamate Receptors in the Mouse Amygdala

“…During the last several decades, a great deal of information has been obtained on the structure, molecular make up, and physiological function of synapses; yet synapses are morphologically and molecularly highly diverse depending on the pre and postsynaptic parent neurons 4 . Only for a handful of synapse types were structure-function studies accomplished so far [5][6][7] . This was mostly due to technical constrains that prevented a precise identification of the nature of the pre-and postsynaptic elements.…”

“…Ultrastructural analysis has provided critical insights into the variability of postsynaptic membrane specializations across distinct synaptic contacts both in terms of synaptic size and content in neurotransmitter receptors 6 , which has a large impact on the strength and plasticity of synaptic transmission. Furthermore, a large body of research indicates that the number of ionotropic glutamate receptors expressed at different types of synapse is regulated in an afferent-and target-dependent fashion [7][8][9][10] .…”