Homeostatic signaling systems are thought to interface with the mechanisms of neural plasticity to achieve stable yet flexible neural circuitry. However, the time course, molecular design, and implementation of homeostatic signaling remain poorly defined. Here we demonstrate that a homeostatic increase in presynaptic neurotransmitter release can be induced within minutes following postsynaptic glutamate receptor blockade. The rapid induction of synaptic homeostasis is independent of new protein synthesis and does not require evoked neurotransmission, indicating that a change in the efficacy of spontaneous quantal release events is sufficient to trigger the induction of synaptic homeostasis. Finally, both the rapid induction and the sustained expression of synaptic homeostasis are blocked by mutations that disrupt the pore-forming subunit of the presynaptic Ca(V)2.1 calcium channel encoded by cacophony. These data confirm the presynaptic expression of synaptic homeostasis and implicate presynaptic Ca(V)2.1 in a homeostatic retrograde signaling system.

Homeostasis is a specialized form of regulation that precisely maintains the function of a system at a set point level of activity. Recently, homeostatic signaling has been suggested to control neural activity through the modulation of synaptic efficacy and membrane excitability ( Davis & Goodman 1998a, Turrigiano & Nelson 2000, Marder & Prinz 2002, Perez-Otano & Ehlers 2005 ). In this way, homeostatic signaling is thought to constrain neural plasticity and contribute to the stability of neural function over time. Using a restrictive definition of homeostasis, this review first evaluates the phenomenological and molecular evidence for homeostatic signaling in the nervous system. Then, basic principles underlying the design and molecular implementation of homeostatic signaling are reviewed on the basis of work in other, simplified biological systems such as bacterial chemotaxis and the heat shock response. Data from these systems are then discussed in the context of homeostatic signaling in the nervous system.

The glutamatergic neuromuscular synapse in Drosophila forms and differentiates into distinct boutons in the embryo and grows by sprouting new boutons throughout larval life. We demonstrate that two axons form approximately 18 boutons on muscles 7 and 6 by hatching and grow to approximately 180 boutons by third instar. We further show that, after synapse formation, the homophilic cell adhesion molecule Fasciclin II (Fas II) is localized both pre- and postsynaptically where it controls synapse stabilization. In FasII null mutants, synapse formation is normal, but boutons then retract during larval development. Synapse elimination and resulting lethality are rescued by transgenes that drive Fas II expression both pre- and postsynaptically; driving Fas II expression on either side alone is insufficient. Fas II can also control synaptic growth; various FasII alleles lead to either an increase or decrease in sprouting, depending upon the level of Fas II.

Transmitter release at the fly neuromuscular junction is abolished in the absence of a scaffold protein.