My laboratory is using the powerful tools of Drosophila genetics to answer basic questions regarding synapse function and development.

1- Molecular mechanisms underlying rapid activity-dependent synaptic plasticity

For decades synaptic plasticity has been associated with fundamental brain functions such as learning and memory. After repeated stimulation, the neuromuscular junction (NMJ) undergoes morphological and electrophysiological changes defined as rapid activity-dependent synaptic plasticity. Such an event requires WNT, a signaling molecule that has been associated with schizophrenia and Alzheimer’s disease. We are aiming at isolating and characterizing the molecular mechanisms downstream of the Wnt signaling that are involved in rapid activity-dependent synaptic plasticity.

2- The molecular control of Synaptic Homeostasis

My laboratory is also exploring how homeostatic signaling can modulate synaptic release. Homeostasis is a form of feedback regulation that precisely maintains the function of a system at a set point level of activity. Within the nervous system, homeostatic signaling systems are thought to constrain plasticity to ensure neural activity will remain stable over time. As such, homeostatic mechanisms are thought to be the mechanisms that prevent the nervous system to fall into chaos and impairment of such mechanisms has been hypothesized to be responsible for epilepsy. However, the molecular mechanisms of homeostasis in the nervous system are virtually unknown. Homeostatic control of neuronal activity has been shown to occur in the CNS and PNS of both vertebrates and invertebrates following perturbation of neuron or muscle excitability. Homeostatic regulation of synaptic strength has been demonstrated at the Drosophila (NMJ). The Drosophila NMJ is a glutamatergic synapse. Manipulations that decrease the sensitivity of postsynaptic glutamate receptors (GluR), 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.

We are now attempting to characterize molecules, ranging from transcription factor to ion channel, necessary to synaptic compensation.

3- Physiological and molecular consequences of environmental change on the nervous system of Drosophila melanogaster.
This project assesses the consequences of environmental change on synaptic development, function and plasticity in Drosophila.  We first focused on the effect of temperature on synaptic development and determined that there is a temperature-dependence of synaptic growth (Synapses from animals grown at 30°C are twice as big as synapses from animals grown at 15°C). We are now trying to identify and characterize the molecular mechanisms underlying this temperature-dependence of synaptic growth.The second aspect of this research consists in asking whether the contaminants found in Puerto Rican rivers can affect the synaptic development, function or plasticity of Drosophila.