| Description |
The adult nervous system is plastic and undergoes activity dependent alterations, which are essential for behaviors such as learning and memory. Paramount to plasticity is the expeditious insertion and removal of synaptic receptors; however, the molecular mechanism(s) that regulate the abundance of receptors at synapses are poorly understood. Recently, we identified a Wnt signaling pathway that increases neurotransmitter receptor levels by specifically augmenting the translocation of one class of acetylcholine receptors (AChRs) at adult synapses. We found that mutations in CWN-2 (Wnt ligand), LIN-17 (Frizzled), CAM-1 (Ror receptor tyrosine kinase), or DSH-1 (disheveled) result in similar subsynaptic accumulations of the a7 AChR homolog ACR-16 in C. elegans. Secondary to accumulation of ACR-16 receptors in subsynaptic membranes is a consequent reduction in synaptic current, and anticipated behavioral defects. Interestingly, perturbation of Wnt signaling results in decreased surface expression and mobility of ACR-16/a7 at synapses. Transient expression and genetic experiments revealed that novel LIN-17/CAM-1 heteromeric receptors regulate ACR-16/a7 translocation to synapses. Using an optogenetic nerve stimulation paradigm, we demonstrate that increased neural activity induces plastic changes in ACR-16/a7 receptor localization and current, and that plasticity is dependent on Wnt signaling. We are currently assessing which subsynaptic membrane pools contribute to ACR-16/a7 translocation in response to increased synaptic activity, and if SNARE complexes regulate this process. We hypothesize that our findings will have direct relevance to ongoing studies of activity mediated receptor translocation in the vertebrate nervous system. |
