Physiological brain temperature is an important determinant for neuronal functions, and it is well established that changes in temperature have dynamic influences on brain neuronal excitabilities. We have clearly revealed that a thermo-sensor TRPV4 (activated above 34°C) is activated by physiological temperature in hippocampal neurons and thereby controls their excitability. Therefore, if local brain temperature could dynamically elevate depending on the neuronal activities, a thermo-sensor TRPV4 can enhance electrical excitability in neurons, and might lead to hyperexcitability. In this study, we focused on epilepsy, since it was caused by hyperexcitability of neurons. We generated a model of partial epilepsy by utilizing kindling stimuli in ventral hippocampus of wild type (WT) or TRPV4KO mice, and measured electroencephalogram (EEG). The frequencies of epileptic EEG in WT mice were significantly larger than those in TRPV4KO mice. These results strongly indicate that TRPV4 activation is involved in disease progression of epilepsy. We expected that the disease progression enhanced hyperexcitability, and lead to hyperthermia in the epileptogenic zones. To confirm it, we developed a new device to measure exact brain temperature only in restricted local area. From the recording results by the new device, we revealed that the brain temperatures in epileptogenic zones were dramatically elevated compared with normal regions. Furthermore, we demonstrated that the temperature elevation was critical for disease progression.