Abstract Major depressive disorder (MDD) is one of the most chronic disease and life-threatening 
illnesses globally. However, mainstay medications do not provide sufficient relief for 
depressive patients with MDD. Thus, there is an urgent need for the development of analysis 
methods that allow drug screening and observation of phenotypes. We developed a tiny 
microneedle electrode block module called the Toyohashi probe, which can be inserted into 
a mouse brain with minimal invasiveness using the vapor–liquid–solid method. Photo
response was measured in the primary visual cortex of Nrf2 knockout (KO) mice using the 
Toyohashi probe. We then successfully identified characteristic electrophysiological 
phenotypes, such as abnormal excitability of neurons and higher firing frequency and spikes, 
in Nrf2 KO mice. In conclusion, our new microneedle electrode can be used in vulnerable 
disease model mice to record stable neuronal activity stably in vulnerable disease model 
mice and observe characteristic phenotypes as indicators for drug efficacy.
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