Carihann Dominicci-Cotto and Bruno Marie

Institute of Neurobiology, University of Puerto Rico, Medical Science Campus;

Department of Anatomy and Neurobiology


Synapses are shaped by plastic events that promote or limit changes in synaptic strength.

Modifications in synaptic strength due to electrical activity are often accompanied by structural changes in synapse shape and number. At the Drosophila neuromuscular junction (NMJ) activitydependent plasticity is characterized by the apparition of new synaptic structures after repeated stimulation. Our lab recently showed that these activity-dependent modifications are regulated presynaptically by Cortactin, a cortical actin binding protein, involved in regulating cytoskeletal dynamics and controlled by the Wnt/wingless (wg) signaling. Although the wg canonical pathway has been implicated in activity-dependent synaptic plasticity, it is still unclear whether the wg planar cell polarity pathway (PCP) is necessary for this phenomenon. We asked whether core molecules of the wg PCP pathway, which regulate cytoskeletal dynamics, can be involved in this process. The wg PCP pathway is composed of a series of small GTPases (Rac, Rho and Cdc42) which are downstream of disheveled (dsh) and upstream of JNK. Here, we looked at the appearance of de novo boutons formation after repeated stimulation in mutants and animals expressing the dominant-negative or constitutively-active form of some members of the PCP pathway. We found that dsh1 mutants, which contain a PCP-specific mutation, had hindered plasticity after stimulation, suggesting that the PCP pathway has a role in this plasticity. We also studied diablo (dbo), a molecule that interacts with dsh to promote the PCP pathway; dbo mutants showed a reduction in the formation of new boutons upon stimulation. We also found that late expression of constitutively-active Rac1 and dominant-negative Rho1 resulted in over-plastic synapses. In contrast, altering Cdc42 function did not affect activity-dependent synaptic plasticity.

We hypothesize that, like for growth cone formation, Rac1 promotes protrusions formation during activity-dependent plasticity, while Rho1 is able to mediate retractions. In addition, we present data suggesting that JNK activity can also affect activity-dependent plasticity. Taken together our data demonstrate that the PCP pathway is essential to the regulation of activity-dependent synaptic plasticity.

Acknowledgments: NIH-RISE (R25-GM061838) and NIH-COBRE (2P20GM103642)

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