Venue: Centre Broca
Juan Garcia Ruiz
Neurocentre Magendie
Thesis supervisor: Aude Panatier
Study of the respective role of glucose and lactate on excitability and basal synaptic transmission in adult rat somatosensory system
Abstract
The brain represents 2% of body weight but consumes 20% of the body’s glucose: approximately 80% is used by neurons and 20% by astrocytes and other glial cells. While neurons were long thought to rely exclusively on glucose via GLUT3-dependent uptake, growing evidence highlighted an important role for astrocyte-derived lactate as an energy source. Astrocytes, positioned between blood vessels and synapses, take up glucose and convert it into lactate. Lactate is then released via MCT1/MCT4 transporters and taken up by neurons through MCT2 to generate ATP. Understanding when and how neurons switch between glucose and lactate remains a fundamental question in brain energetics. Neuronal activity spans a spectrum of energy demands. Action potentials represent a comparatively moderate energy load, whereas synaptic transmission is highly energy demanding and accounts for approximately 70% of the total signaling energy budget, largely due to the maintenance and restoration of ion gradients dissipated during neuronal communication.
Our aim is to determine whether the choice of energy substrate depends on neuronal energy demand. In addition to its role in ATP production, we also investigated whether glucose may support neuronal function through alternative metabolic pathways, such as the pentose phosphate pathway (PPP), which contributes to redox homeostasis and biosynthetic processes. To address these questions, we used a viral approach to downregulate either the neuronal glucose transporter GLUT3, the neuronal lactate transporter MCT2, or the astrocytic lactate transporters MCT1/MCT4 in the rat somatosensory cortex. During whole-cell patch-clamp recordings, neuronal excitability was assessed by firing frequency, while basal synaptic transmission was evaluated through miniature excitatory postsynaptic events. Neuronal excitability appears to depend specifically on glucose, showing a gatekeeper role involving non-energetic metabolic functions through the PPP rather than ATP production itself. On the other hand, both glucose and lactate are involved in supporting basal synaptic transmission. These findings reveal distinct and complementary roles of glucose and lactate in neuronal function.
Jury
Président : Jérôme Baufreton, Directeur de recherche, Institut de Maladies Neurodégénératives, Bordeaux
Rapportrice : Armelle Rancillac, Chargée de recherche, Centre Interdisciplinaire de Recherche en Biologie, Paris
Rapporteur : Pierre-Yves Plaçais, Directeur de recherche, École Supérieure de Physique et de Chimie Industrielles, Paris
Directrice : Aude Panatier, Directrice de recherche, Neurocentre Magendie, Bordeaux