Size matters: formation and function of giant synapses

Abstract

This symposium took place as a satellite of the Society for Neuroscience Meeting in New Orleans on Friday 12 October 2012, hosted by the Neuroscience Center of Excellence at Louisiana State University and sponsored by The Journal of Physiology and The Physiological Society. The meeting drew together several neuroscience communities with differing perspectives on development and function at large synapses in both mammalian and invertebrate nervous systems, including both CNS synapses and peripheral synapses of the neuromuscular junction (NMJ) and considering both pre- and postsynaptic interfaces. For a synapse, size is a clear predictor of its potential power in influencing the target (Petrof & Sherman, 2013). In most cases, single neurons integrate information from many thousands of synapses, but in some cases (such as the NMJ and the calyx of Held) a very high proportion of the synaptic input arises from one dominant axon terminal. Synaptic physiologists have favoured giant synapses for their accessibility, and much of our knowledge about synaptic transmission has been learned from these giant synapses, including the squid giant synapse and the frog NMJ. The unique accessibility of the NMJ has allowed developmental neurobiologists to elucidate the key factors required for synapse assembly. In recent times, a combination of technical breakthroughs in genetic labelling and imaging methods has illustrated that big is also beautiful, as evidenced by studies in which the formation of individual synapses can be followed in vivo. This series of symposium reviews focuses on the formation and then the function of large synapses across a variety of model systems. They include electrophysiological and imaging studies, with presentations about giant synapses from the NMJ to the retina, and from hippocampus to brainstem. The first review, from Tian & Wu (2013), considers the fly and worm model organisms to examine the molecular mechanisms by which ubiquitination regulates synaptogenesis and axonal responses after nerve injury. The ubiquitination cascade, in conjunction with autophagy, dynamically and specifically controls protein turnover to ensure normal synaptic development, clearance of injured distal axons and regeneration of proximal axons. Holcomb et al. (2013) have exploited the new scanning block-face electron microscopy to reconstruct both synaptic and postsynaptic targets of the calyx of Held synapse in order to ask fundamental questions about the origins of neuronal polarity and the ways in which this can guide the earliest stages of synapse formation. The developmental theme continues with a review of cerebellar climbing fibre synapse development, a well-established and elegant mode of synapse elimination in the mammalian CNS. This model is used here by Kano and colleagues (2013) to demonstrate how regulation of calcium transients is involved in the competitive strengthening or weakening of the synapse and implicated in later phases of elimination. From a functional perspective, synapses with differing synaptic strengths within the same network can perform differing functions. Petrof & Sherman (2013) explored the unique features of two classes of thalamocortical synapses with distinct integrative roles; large glutamatergic synapses predominate in transmission of information, while small glutamatergic synapses serve to modulate cortical function. The series concludes with reviews on transmitter release from some of the most intensely studied synaptic terminals. The strength and reliability of transmission at the NMJ is presented from both amphibian and mammalian viewpoints by Meriney & Dittrich (2013). Then the highly specialized sensory synapses of the ear and eye, which are adapted for high levels of exocytosis, are considered from the perspective of their respective neural codes. Kim et al. (2013) suggest that these data support the notion that single calcium channels can trigger exocytosis of multiple vesicles. The theme of contrasting form and function within synaptic structures is continued by Delvendahl et al. (2013) with the mossy fibre terminals of the hippocampus and cerebellum, where the low release probability of hippocampal mossy fibres contrasts with the high release probability of cerebellar mossy fibres. Finally, Neher & Taschenberger (2013) review the recent literature on intracellular calcium binding at the calyx of Held and present some unresolved questions about the mechanisms regulating the time course of the calcium transient.