Lab focus
My laboratory seeks to provide answers to long-standing challenges in the field of brain metabolism like: How do neurons upregulate their energy metabolism to cope with moment-to-moment energy demands? What are the mechanisms that ensure the metabolic tuning in different cell types-for example, neurons and astrocytes? We also address the fuel flexibility of neural cells, as well as the potential metabolic cooperation among them. In addition, we investigate the effects that systemic metabolism exerts on the brain, mainly through hormones and circulating metabolites. We are particularly interested in the potential role of brain insulin signaling on the hypometabolic states associated with cognitive decline, which are hallmarks of the natural process of aging, as well as several neurodegenerative and metabolic diseases.
To achieve our goals, we visualize the metabolism of neural cells in live brain tissue using genetically encoded fluorescent biosensors in combination with 2-photon microscopy and fluorescence lifetime imaging. Our approaches are designed to perform direct, quantitative measurements of real-time dynamics of several metabolites (e.g. glucose, lactate, NADH/NAD+, ATP/ADP, etc), with cellular and subcellular resolution. We complement these studies with functional approaches that include calcium imaging, electrophysiology, and behavioral tests.
Why it matters
Energy consumption in the brain accounts for almost 20% of the body’s energy expenditure at rest, similar to cardiac or skeletal muscle. However, contrary to these tissues, the brain almost exclusively relies on glucose utilization, and it only has scarce energy reserves in the form of astrocytic glycogen. Energy needs in the brain are particularly high and highly dynamic in neurons, due to repetitive fluctuations in their membrane potential and the events related to neurotransmission. Therefore, keeping the cellular metabolic infrastructure in good repair is essential for proper brain function. We have vast knowledge about the metabolites and pathways involved in brain energy metabolism, however, it is still puzzling how neural cells integrate intrinsic and extrinsic signals to upregulate these pathways on demand. More importantly, metabolic failure has been associated with cognitive aging, as well as with synaptic dysfunction—and neuronal demise—in several neurological disorders.
Our work is also motivated by several metabolic interventions that are currently tested for tackling age-related, or pathological, cognitive decline. Although broad in nature, calorie restriction, intermittent fasting, NAD-precursor supplementation, or hormonal therapy, all highlight the untapped therapeutic potential of targeting brain metabolism to improve learning and memory. My research program is focused on understanding the cellular metabolic responses to stimulation in the hippocampus, a brain area that allows us to navigate a new environment, store new information and retrieve information of previous experiences. Ultimately, our goal is to identify potential metabolic targets for interventions aimed at a healthy brain aging.