LABORATORY OF INVERTEBRATE NEUROBIOLOGY

Research lines

• Molecular Basis of Excitation/Inhibition Imbalance in C. elegans

Excitatory and inhibitory neurotransmission must be maintained in a delicate balance to ensure the proper functioning of the nervous system. Alterations in this balance have been associated with a variety of neurological and neurodevelopmental disorders. Using the C. elegans neuromuscular system as an experimental model, we study the molecular mechanisms that regulate the coordination between excitatory cholinergic and inhibitory GABAergic signaling.
Through genetic, pharmacological, behavioral, microscopy, and optogenetic approaches, we investigate how mutations in genes orthologous to human genes associated with neurological disorders affect nervous system development and function. Recently, we have investigated the role of daf-18, the C. elegans ortholog of PTEN, in neurodevelopment and excitation/inhibition balance, as well as the therapeutic potential of a β-hydroxybutyrate-enriched diet to ameliorate some of the defects associated with this mutation.
We are currently working to elucidate the mechanisms underlying other genes linked to autism spectrum disorders and different forms of excitation/inhibition imbalance, while also identifying potential therapeutic strategies to modulate these alterations.
Principal Investigators: Diego Rayes and María José De Rosa

• Neural Control of Systemic Processes in C. elegans

Organisms must continuously integrate information from the environment and their internal state to coordinate appropriate physiological and adaptive responses. Our goal is to understand how the nervous system regulates systemic responses to different environmental challenges at the molecular and cellular levels.
Recently, we identified a novel brain–gut communication pathway in C. elegans that helps explain how acute stress affects the organism’s response to other environmental challenges. We found that tyramine, a neurotransmitter functionally related to catecholamines in mammals, acts as a state-dependent neural signal that regulates the balance between acute and long-term stress responses by coordinating the release of insulin-like peptides from the intestine.
We are currently investigating the intracellular mechanisms that control the release of these peptides and exploring how the nervous system senses nutritional status and uses this information to regulate adaptive strategies, including both behavioral and physiological responses. Given the high evolutionary conservation of these mechanisms, our studies contribute to the understanding of similar processes in more complex organisms, including mammals.
Principal Investigator: Diego Rayes

• C. elegans as a Platform for Studying Neurodegenerative Diseases and Identifying Novel Therapeutic Strategies

Neurodegenerative diseases, such as Huntington’s, Alzheimer’s, and Parkinson’s diseases, are characterized by the progressive loss of neuronal function and, frequently, by the accumulation of misfolded or aggregated proteins. Although these disorders are highly complex, many of the cellular mechanisms involved in their progression are evolutionarily conserved.
We use C. elegans models of neurodegenerative diseases to investigate the molecular mechanisms underlying impaired proteostasis, oxidative stress, and neurodegeneration. We study protective cellular processes, including autophagy, stress responses, and mechanisms regulated by transcription factors such as DAF-16/FOXO, with the aim of understanding how these pathways can modulate proteotoxic damage.
In this research line, we have identified both synthetic compounds (imidazole derivatives) and natural compounds (such as geraniol) capable of modulating toxic protein aggregation, and we are currently exploring new strategies to better understand and target the pathological mechanisms underlying neurodegenerative diseases.
Principal Investigator: María José De Rosa