Glycolytic Specialization Shapes Neuronal Physiology and Function in vivo

Area of Science:

• Neuroscience
• Cellular Metabolism
• Systems Biology

Background:

• Neurons exhibit diverse functions with varying energy needs, but the in vivo matching of metabolic pathways to neuronal function is not well understood.
• Understanding neuron-specific metabolism is crucial for deciphering how distinct cellular functions are supported.
• Chemosensory neurons in C. elegans provide a model system to investigate functional divergence.

Purpose of the Study:

• To investigate how energy-metabolic pathways are matched to distinct neuronal functions in vivo.
• To determine the role of glycolysis in shaping the biophysical properties and functional identity of individual neurons.
• To elucidate the functional consequences of metabolic asymmetry in sister neurons.

Main Methods:

• Utilized metabolic imaging and metabolic network modeling in C. elegans.
• Performed electrophysiology measurements to assess neuronal properties.
• Investigated the effects of impairing glycolysis on neuronal function and calcium responses.

Main Results:

• Demonstrated asymmetric glycolytic flux between two sister chemosensory neurons (ASEL and ASER) in C. elegans, with ASER showing high glycolysis and ASEL showing low glycolysis.
• Showed that elevated glycolysis in ASER supports a hyperpolarized resting potential, low input resistance, and rapid repolarization, contributing to its distinct function.
• Found that impairing glycolysis disrupted these electrophysiological specializations and selectively affected ASER's calcium responses, while leaving ASEL largely unaffected.

Conclusions:

• Neuron-specific glycolytic programs are essential for establishing and maintaining core biophysical properties.
• Metabolism actively determines neuronal physiology and functional identity in vivo.
• Asymmetric metabolic strategies allow functionally divergent sister neurons to perform specialized roles.