Blitzer, R. | Search bioRxiv

bioRxiv2026

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.

bioengineering↗

bioRxiv2017

Experience-induced forgetting by WT1 enables learning of sequential tasks.

Under physiological conditions, strength and persistence of memory must be regulated in order to produce behavioral flexibility. In fact, impairments in memory flexibility are associated with pathologies such as post-traumatic stress disorder or autism; however the underlying mechanisms that enable memory flexibility are still poorly understood. Here we identified the transcriptional repressor Wilms Tumor 1 (WT1) as a critical synaptic plasticity regulator that decreases memory strength, promoting memory flexibility. WT1 was activated in the hippocampus following induction of long-term potentiation (LTP) or learning. WT1 knockdown enhanced CA1 neuronal excitability, LTP and long-term memory whereas its over-expression weakened memory retention. Moreover, forebrain WT1-deficient mice showed deficits in both reversal, sequential learning tasks and contextual fear extinction, exhibiting impaired memory flexibility. We conclude that WT1 limits memory strength or promotes memory weakening, thus enabling memory flexibility, a process that is critical for learning from new experience.

neuroscience↗