Calcium-induced upregulation of energy metabolism heats neurons during neural activity

Abstract

Cellular temperature affects every biochemical reaction, underscoring its critical role in cellular functions. In neurons, temperature not only modulates neurotransmission but is also a key determinant of neurodegenerative diseases. Considering that the brain consumes a disproportionately high amount of energy relative to its weight, neural circuits likely generate a lot of heat, which can increase cytosolic temperature. However, the changes in temperature within neurons and the mechanisms of heat generation during neural excitation remain unclear. In this study, we achieved simultaneous imaging of Ca²⁺ and temperature using the genetically encoded indicators, B-GECO and B-gTEMP. We then compared the spatiotemporal distributions of Ca²⁺ responses and temperature. Following neural excitation induced by veratridine, an activator of the voltage-gated Na⁺ channel, we observed an approximately 2 °C increase in cytosolic temperature occurring 30 s after the Ca²⁺ response. The temperature elevation was observed in the non-nuclear region, while Ca²⁺ increased throughout the cell body. Moreover, this temperature increase was suppressed under Ca²⁺-free conditions and by inhibitors of ATP synthesis. These results indicate that Ca²⁺-induced upregulation of energy metabolism serves as the heat source during neural excitation.

Keywords: ATP synthesis; Energy consumption; Glycolysis; Mitochondria; Temperature imaging; Thermogenesis.