Fast-response micromachined thermocouple microprobe for localized thermometry of hippocampal slices during high-frequency stimulation

Micromachined thermocouple microprobes provide a promising approach for localized temperature sensing in biologically relevant microenvironments because of their small sensing area, low thermal mass, and rapid response. In this work, we applied fast-response micromachined thermocouple probes to measure localized temperature transients in mouse hippocampal brain slices during intense synaptic activation. The probes were positioned within the tissue to record real-time temperature changes during high-frequency electrical stimulation (100 Hz) of Schaffer collateral inputs. At a bath set-point of 23 ± 1 °C, stimulation produced a local temperature increase with a peak temperature increase of 0.54 ± 0.07 °C ( n = 4). In contrast, after pharmacological blockade of action potential generation with tetrodotoxin, the same stimulation protocol produced no measurable temperature rise. These measurements demonstrate that the micromachined thermocouple platform can resolve small, localized, activity-dependent thermal signals in neural tissue under physiologically relevant stimulation conditions. The results also indicate that high-frequency neuronal firing and synaptic transmission transiently elevate local brain temperature, consistent with increased metabolic energy consumption. This study highlights the utility of micromachined thermocouple sensors for direct thermometry in neural preparations and supports their broader use for spatially localized thermal measurements in complex biological systems.