Methcathinone Increases Visually-evoked Neuronal Activity and Enhances Sensory Processing Efficiency in Mice

 Jun Zhou1,2 · Wen Deng1,2 · Chen Chen1,2 · Junya Kang1,2 · Xiaodan Yang1,2 · Zhaojuan Dou1,2 · Jiancheng Wu3  · Quancong Li3  · Man Jiang4  · Man Liang3,5 · Yunyun Han1,2,5
1 Department of Neurobiology, School of Basic Medicine and Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China 
2 Institute for Brain Research, Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology, Wuhan 430030, China 
3 Department of Forensic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China 
4 Department of Physiology, School of Basic Medicine and Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China 
5 Key Laboratory of Forensic Toxicology, Ministry of Public Security, Beijing 100192, China

Abstract
Methcathinone (MCAT) belongs to the designer drugs called synthetic cathinones, which are abused worldwide for recreational purposes. It has strong stimulant effects, including enhanced euphoria, sensation, alertness, and empathy. However, little is known about how MCAT modulates neuronal activity in vivo. Here, we evaluated the effect of MCAT on neuronal activity with a series of functional approaches. C-Fos immunostaining showed that MCAT increased the number of activated neurons by 6-fold, especially in sensory and motor cortices, striatum, and midbrain motor nuclei. In vivo single-unit recording and two-photon Ca2+ imaging revealed that a large proportion of neurons increased spiking activity upon MCAT administration. Notably, MCAT induced a strong de-correlation of population activity and increased trial-to-trial reliability, specifically during a natural movie stimulus. It improved the information-processing efficiency by enhancing the single-neuron coding capacity, suggesting a cortical network mechanism of the enhanced perception produced by psychoactive stimulants.

Keywords
Methcathinone; Synthetic psychoactive substance; In vivo single-unit recording; imaging; Ca2+ Nucleus accumbens; Visual cortex