Abstract
The functional properties of neural circuits are defined by the patterns of synaptic connections between their partnering neurons, but the mechanisms that stabilize circuit connectivity are poorly understood. We systemically examined this question at synapses onto newly characterized dendritic spines of C. elegans GABAergic motor neurons. We show that the presynaptic adhesion protein neurexin/NRX-1 is required for stabilization of postsynaptic structure. We find that early postsynaptic developmental events proceed without a strict requirement for synaptic activity and are not disrupted by deletion of neurexin/nrx-1. However, in the absence of presynaptic NRX-1, dendritic spines and receptor clusters become destabilized and collapse prior to adulthood. We demonstrate that NRX-1 delivery to presynaptic terminals is dependent on kinesin-3/UNC-104 and show that ongoing UNC-104 function is required for postsynaptic maintenance in mature animals. By defining the dynamics and temporal order of synapse formation and maintenance events in vivo, we describe a mechanism for stabilizing mature circuit connectivity through neurexin-based adhesion.
Highlights
The capabilities of neural circuits to perform specific functions arise from the patterns of synaptic connections between their partnering neurons
The nervous system is composed of networks of interconnecting cells called neurons
It is crucial to gain a complete understanding of the steps in assembly of a developing synapse, and of the mechanisms involved in synapse maturation and maintenance
Summary
The capabilities of neural circuits to perform specific functions arise from the patterns of synaptic connections between their partnering neurons. The organization of these connections is circuit-specific and established through a complex process that involves the coordinated assembly and maturation of specialized pre- and postsynaptic structures on appropriate partnering neurons, and their maintenance in the mature nervous system. Genetic studies have identifed numerous mutations that alter circuit connectivity or affect the overall structural organization of synapses [1,2,3]. For many of the synapse-associated proteins affected by these mutations, we do not yet have a mechanistic understanding of their roles in establishing synaptic connections, or how their disruption may lead to alterations in synapse stability. Gaining an enhanced understanding of the sequence of events involved in synapse assembly, maturation, and maintenance, and their relative timing in vivo is critical for addressing these questions
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