Neurons are capable of undergoing dynamic remodeling. During development their capacity of dynamic structural changes supports the construction of functional neuronal circuits. In the course of adult life, neurons retain the capability to undergo active structural changes. These support plasticity, including learning and the formation of lasting memories, and also counteract circuit destabilization and degeneration. Utilizing the classic genetic model organism Drosophila, we study the cellular mechanisms that support neuronal dynamics during development and during the animal’s adult life. Our hypothesis is that shared molecular mechanisms control dynamics at both stages.
Neurons receive information at their dendritic input compartment. The morphology of dendrites defines the neuron’s input region and contributes to initial processing of incoming information. Aberrant dendrite organization is a typical trait of human syndromes leading to mental retardation. In addition, dendrite destabilization is an early phenotype of neurodegenerative phenomena. We thus investigate the cellular mechanisms that define the complex and neuron-type specific morphology of dendrites. In the past years, we have identified a cascade of regulatory events that leads to dendrite branch initiation. Furthermore, we have recently discovered that the synthesis of lipids required for dendrite tree elaboration is cell-autonomously carried out and regulated by the neurons. We currently focus on how cytoskeletal regulation and metabolic factors control neuronal differentiation.
Once differentiation is completed, neurons retain some capacity for plastic remodeling, which underlies fundamental functions, including learning. To understand the cellular modifications that support learning we have characterized to a great extent a circuit involved in the formation of olfactory associative memories in the fly brain. Here, we can now visualize and manipulate pre- and postsynaptic elements involved in learning. We have recently shown that this circuit undergoes structural and functional modifications during memory consolidation. We will thus concentrate our efforts in understanding the underlying molecular mechanisms and how these are modified by cognitive decline during ageing. Finally, we have analyzed in detail the synaptic organization of key synapses in this circuit. Based on previous studies from our lab, we will use this information to address the interplay between synaptic function and axon maintenance.