Micromachined Thermocouple Microprobe for Real-Time Thermometry of Hippocampal Slices during High-Frequency Stimulation

Neuronal activity is energetically demanding and generates heat as a metabolic byproduct. Here we investigated localized temperature changes in mouse hippocampal brain slices during intense synaptic activation. Using fast-response thermocouple microprobes placed in the tissue, we measured real-time temperature fluctuations during high-frequency (100 Hz) electrical stimulation of Schaffer collateral inputs. Stimulation induced a local temperature increase (peak {Delta}T = 0.54 {+/-} 0.07 {degrees}C; n = 4). In contrast, when action potentials were blocked with tetrodotoxin (TTX), the same stimulation produced no measurable temperature rise. These results demonstrate that high-frequency neural firing and synaptic transmission can transiently elevate local brain tissue temperature, presumably due to increased metabolic activity and adenosine triphosphate (ATP) consumption. The hippocampus tolerated these small temperature shifts, but even modest heating could influence neuronal function. Our findings provide direct experimental evidence linking synaptic activity to localized brain heat production, and underscore the importance of considering thermogenesis under stimulation conditions that give rise to forms of synaptic plasticity.