Reducing the expression of the Numb adaptor protein in neurons increases the searching behavior of larvae.

larval crawling is easily-observable and relatively stereotyped. Crawling consists of linear locomotion interrupted by periods when the larvae pause, swing their heads, and change direction (a 'search'). Here we identify Numb, a peripheral membrane adaptor protein, as an important regulator of searching behavior.

Drosophila enabled promotes synapse morphogenesis and regulates active zone form and function.

Background: Recent studies of synapse form and function highlight the importance of the actin cytoskeleton in regulating multiple aspects of morphogenesis, neurotransmission, and neural plasticity. The conserved actin-associated protein Enabled (Ena) is known to regulate development of the Drosophila larval neuromuscular junction through a postsynaptic mechanism. However, the functions and regulation of Ena within the presynaptic terminal has not been determined.

Target-dependent retrograde signaling mediates synaptic plasticity at the Drosophila neuromuscular junction.

Neurons that innervate multiple targets often establish synapses with target-specific strengths, and local forms of synaptic plasticity. We have examined the molecular-genetic mechanisms that allow a single Drosophila motoneuron, the ventral Common Exciter (vCE), to establish connections with target-specific properties at its various synaptic partners. By driving transgenes in a subset of vCE's targets, we found that individual target cells are able to independently control the properties of vCE's innervating branch and synapses.

Retrograde BMP signaling at the synapse: a permissive signal for synapse maturation and activity-dependent plasticity.

At the Drosophila neuromuscular junction (NMJ), the loss of retrograde, trans-synaptic BMP signaling causes motoneuron terminals to have fewer synaptic boutons, whereas increased neuronal activity results in a larger synapse with more boutons. Here, we show that an early and transient BMP signal is necessary and sufficient for NMJ growth as well as for activity-dependent synaptic plasticity. This early critical period was revealed by the temporally controlled suppression of Mad, the SMAD1 transcriptional regulator.

Cracking the combinatorial semaphorin code.

In this issue of Neuron, Wu et al. describe a combinatorial code of repulsive Sema-2a and attractive Sema-2b signaling that mediates mechanosensory axonal guidance, fasciculation, and synaptic target selection within the CNS of Drosophila. Their work exemplifies how a detailed, multilevel molecular-genetic analysis (from molecules to behavior) provides fundamental insights into neural circuit development.

Temperature-dependent developmental plasticity of Drosophila neurons: cell-autonomous roles of membrane excitability, Ca2+ influx, and cAMP signaling.

Environmental temperature is an important factor exerting pervasive influence on neuronal morphology and synaptic physiology. In the Drosophila brain, axonal arborization of mushroom body Kenyon cells was enhanced when flies were raised at high temperature (30 degrees C rather than 22 degrees C) for several days. Isolated embryonic neurons in culture that lacked cell-cell contacts also displayed a robust temperature-induced neurite outgrowth.

Regional calcium regulation within cultured Drosophila neurons: effects of altered cAMP metabolism by the learning mutations dunce and rutabaga.

The dunce (dnc) and rutabaga (rut) mutations of Drosophila affect a cAMP-dependent phosphodiesterase and a Ca(2+)/CaM-regulated adenylyl cyclase, respectively. These mutations cause deficiencies in several learning paradigms and alter synaptic transmission, growth cone motility, and action potential generation. The cellular phenotypes either are Ca(2+) dependent (neurotransmission and motility) or mediate a Ca(2+) rise (action potential generation).