Presynaptic morphogenesis, active zone organization and structural plasticity in Drosophila

Abstract

Effective adaptation of neural circuit function to a changing environment requires many forms of plasticity. Among these, structural plasticity is one of the most durable, and is also an intrinsic part of the developmental logic for the formation and refinement of synaptic connectivity. Structural plasticity of presynaptic sites can involve the addition, remodeling, or removal of pre- and post-synaptic elements. However, this requires coordination of morphogenesis and assembly of the subcellular machinery for neurotransmitter release within the presynaptic neurons, as well as coordination of these events with the postsynaptic cell. While much progress has been made in revealing the cell biological mechanisms of postsynaptic structural plasticity, our understanding of presynaptic mechanisms is less complete.

Endogenous tagging reveals differential regulation of Ca2+channels at single AZs during presynaptic homeostatic potentiation and depression

“…Various forms of adaptive plasticity operate to adjust presynaptic release properties (Regehr, 2012;Kittel and Heckmann, 2016;Jackman and Regehr, 2017;Monday and Castillo, 2017;Van Vactor and Sigrist, 2017). PHP is a conserved mechanism for maintaining synaptic strength within a stable range (Cull-Candy et al, 1980;Frank, 2014;Davis and Muller, 2015).…”

“…At fly NMJs, single Drosophila glutamatergic motorneurons form hundreds of synapses with their postsynaptic muscle targets. These synapses have many presynaptic parallels to excitatory synapses in the mammalian CNS, including molecular composition, ultrastructural organization of AZs, and neurotransmitter release properties (Ackermann et al, 2015;Harris and Littleton, 2015;Zhan et al, 2016;Van Vactor and Sigrist, 2017). Further, functional imaging studies with genetically encoded Ca 2+ indicators have facilitated the investigation of neurotransmission at single synapses of Drosophila motorneurons, revealing a remarkable degree of heterogeneity in release properties between individual AZs (Guerrero et al, 2005;Peled and Isacoff, 2011;Melom et al, 2013;Peled et al, 2014;Akbergenova et al, 2017).…”

Invaginating Presynaptic Terminals in Neuromuscular Junctions, Photoreceptor Terminals, and Other Synapses of Animals

“…One BMP presynaptic receptor, Wit (Wishful Thinking) appears to require a trans-synaptic complex of neurexin and neuroligin for its proper localization and stability, and mutants of the latter two proteins have distinctive ultrastructural defects in the synapse (Banerjee et al 2017). There are numerous other components to NMJ regulation in Drosophila (reviewed in Deshpande and Rodal 2016; Van Vactor and Sigrist 2017); for example, APPL, the Drosophila homolog of p-amyloid precursor protein (APP) helps regulate synapse formation at NMJs (Torroja et al 1999). In summary, the invaginating presynaptic terminal of the larval Drosophila NMJ may be designed specifically to facilitate the precise exchange of several factors that coordinate the rapid growth and function of these NMJs, and this is an essential component of rapid larval growth.…”

The THO Complex Coordinates Transcripts for Synapse Development and Dopamine Neuron Survival

“…They consist of a pre- and postsynapse, which are built from hundreds of proteins (Laßek et al, 2015). While the molecular composition and architecture of pre- and postsynapses has been widely explored (Frank and Grant, 2017; Laßek et al, 2015; Van Vactor and Sigrist, 2017), much less is known, how synaptogenesis is regulated at the level of gene expression. Is there a mechanism that coordinates the expression of functionally related proteins such that they are ready to assemble into higher order structures concomitantly?…”