3D imaging of the central nervous system at the microscopic level is essential to investigate morphological changes of various diseases or to assess the efficacy of a treatment (Denk et Horstman, 2004). However, this 3D exploration of the tissues is very limited because of the small volumes and the opacity of the tissues, which does not allow the passage of the light. Technological advances in biphotonic and light-sheet microscopy together with the development of numerous methods in tissue clearing represent innovative solutions for exploring the organs at the cellular level (Hama H. et al., 2011 ; Chung K. et al., 2013, Chenchen P. et al. 2016). These methods are very promising tools to assess new therapeutic strategies on neurodegenerative diseases developed by our research unit UMR703 using animal models and AAV vector encoding fluorescent proteins.For our study we used Scale, Clarity and uDISCO clearing methods and biphotonic imaging on thick brain sections. Harmonic and fluorescence signals conservation results will be discussed
