The Drosophila Fragile X Syndrome model has long generated insights into this devastating neurological disease state. A recent study of olfactory neural circuitry shows that decreased lateral inhibition onto projection neurons relaying sensory input into higher brain centers causes impaired behavior. Read More

Evidence accumulating over the past 15 years soundly refutes the dogma that the Drosophila nervous system is hardwired. The preponderance of studies reveals activity-dependent neural circuit refinement driving optimization of behavioral outputs. We describe developmental, sensory input-dependent plasticity in the brain olfactory antennal lobe, which we term long-term central adaption… Read More

The multiple galactosemia disease states manifest long-term neurological symptoms. Galactosemia I results from loss of galactose-1-phosphate uridyltransferase (GALT), which converts galactose-1-phosphate + UDP-glucose to glucose-1-phosphate + UDP-galactose. Galactosemia II results from loss of galactokinase (GALK), phosphorylating galactose to galactose-1-phosphate. Galactosemia III results from the loss of UDP-galactose 4'-epimerase (GALE), which interconverts UDP-galactose and UDP-glucose,… Read More

Congenital disorders of glycosylation (CDGs) constitute a rapidly growing family of human diseases resulting from heritable mutations in genes driving the production and modification of glycoproteins. The resulting symptomatic hypoglycosylation causes multisystemic defects that include severe neurological impairments, revealing a particularly critical requirement for tightly regulated glycosylation in the nervous… Read More

Neural circuit optimization occurs through sensory activity-dependent mechanisms that refine synaptic connectivity and information processing during early-use developmental critical periods. Fragile X Mental Retardation Protein (FMRP), the gene product lost in Fragile X syndrome (FXS), acts as an activity sensor during critical period development, both as an RNA-binding translation regulator… Read More

Aversive olfactory classical conditioning has been the standard method to assess Drosophila learning and memory behavior for decades, yet training and testing are conducted manually under exceedingly labor-intensive conditions. To overcome this severe limitation, a fully automated, inexpensive system has been developed, which allows accurate and efficient Pavlovian associative learning/memory… Read More

Synaptogenesis requires orchestrated intercellular communication between synaptic partners, with trans-synaptic signals necessarily traversing the extracellular synaptomatrix separating presynaptic and postsynaptic cells. Extracellular matrix metalloproteinases (Mmps) regulated by secreted tissue inhibitors of metalloproteinases (Timps), cleave secreted and membrane-associated targets to sculpt the extracellular environment and modulate intercellular signaling. Here, we test… Read More

The control of new protein synthesis provides a means to locally regulate the availability of synaptic components necessary for dynamic neuronal processes. The fragile X mental retardation protein (FMRP), an RNA-binding translational regulator, is a key player mediating appropriate synaptic protein synthesis in response to neuronal activity levels. Loss of… Read More

Mind-the-Gap (MTG) is required during synaptogenesis of the Drosophila glutamatergic neuromuscular junction (NMJ) to organize the postsynaptic domain. Here, we generate MTG::GFP transgenic animals to demonstrate MTG is synaptically targeted, secreted, and localized to punctate domains in the synaptic extracellular matrix (ECM). Drosophila NMJs form specialized ECM carbohydrate domains, with… Read More

In many nervous systems, the establishment of neural circuits is known to proceed via a two-stage process; (1) early, activity-independent wiring to produce a rough map characterized by excessive synaptic connections, and (2) subsequent, use-dependent pruning to eliminate inappropriate connections and reinforce maintained synapses. In invertebrates, however, evidence of the… Read More