Molecular Mechanisms Underlying Synaptic Homeostasis
The main objective of the lab is to identify molecules and mechanisms essential for synaptic homeostasis.
There is evidence that homeostatic signaling systems can regulate neuronal excitability through modulation of synaptic transmission or ion channel abundance. However, the molecular mechanisms responsible for the homeostatic regulation of neural function remain poorly understood. It has also been hypothesized that defective homeostatic signaling could contribute to the cause or progression of neurological disease. However, molecular characterization of homeostatic signaling will be necessary before clear links to neurological disease can be established.
Homeostatic regulation of synaptic strength has been demonstrated at the Drosophila Neuromuscular Junction (NMJ). The DrosophilaNMJ is a glutamatergic synapse. Manipulations that decrease the sensitivity of postsynaptic glutamate receptors, cause a compensatory, homeostatic increase in presynaptic neurotransmitter release (see diagram). This increase in presynaptic neurotransmitter release precisely counteracts the decrease in postsynaptic receptor sensitivity allowing normal muscle contraction.
In a large-scale screening effort, we identified two genes, the gene gooseberry and the gene slowpoke as being necessary for synaptic homeostasis at the Drosophila NMJ. We are now characterizing the function of these two molecules in the modulation of synaptic release.
Our research approaches include Drosophila genetics, molecular biology, synaptic electrophysiology and live imaging.
List of current research projects with a brief description of each.
- The role of the BK channel slowpoke in synaptic transmission and homeostatic modulation
- The role of the transcription factor gooseberry in consolidating synaptic homeostasis
Marie B, Pym E, Davis GW (submitted) Synaptic Homeostasis is Consolidated by the Cell Fate Gene gooseberry; a Drosophila pax-3/7homologue.
Booth D, Marie B, Domenici P, Blagburn J, Bacon JP (2009) Transcriptional control behavior: Engrailed knockout changes cockroach escape trajectories. Journal of Neuroscience. 29: 7181-7190.
Marie B, Sweeney ST, Poskanzer KE, Roos J, Kelly RB, Davis GW (2004) Dapl60/intersectin scaffolds the periactive zone to achieve high-fidelity endocytosis and normal synaptic growth. Neuron. 43: 207-219.
Marie B and Blagburn JM (2003). Differential roles of Engrailed paralogs in determining sensory axon guidance and synaptic target recognition. Journal of Neuroscience 23: 7854-7862.
Soto I, Marie B, Baro D.J, Blanco R.E (2003). FGF-2 modulates the expression and distribution of GAP-43 in frog retinal ganglion cells after optic nerve injury. Journal of Neuroscience Research 73: 507-517.
Marie B, Cruz-Orengo L and Blagburn J.M (2002). Persistent Engrailed expression is required to determine sensory axon trajectory, branching, and target choice. Journal of Neuroscience 22: 832-841.
Marie B, Bacon J.P and Blagburn JM. (2000). Double-stranded RNA interference shows that Engrailed controls the synaptic specificity of identified sensory neurons.Current Biology
Marie B and Bacon J.P (2000). Two engrailed-related genes in the cockroach: cloning, phylogenetic analysis, expression and isolation of spliced variants.Genes and Evolution 210: 436-448.