Brain-wide Quantification of Inflammation and Neural Activity

To better establish the link between neural activity, inflammation and behavior, new tools are needed that capture brain-wide histological patterns at cellular resolution. By combining advances in tissue clearing, light sheet imaging, computational alignment of anatomy, machine learning-based image processing, and novel statistical methods, our imaging platform quantifies molecular markers of neuronal, monocyte, and microglial activity with unprecedented resolution and fidelity in the mouse brain. In this talk, complete approaches for three example applications are described:

• Detection of a regional focus for brain monocyte infiltration after infection with Toxoplasma gondii
• Brain-wide neural activity mapping in response to recent experience
• Morphological quantification of microglial activity induced by coronavirus infection
  
  

Key Learnings:

• Optimization of the iDISCO+ clearing method for whole-brain immunostaining using a ZEISS lightsheet microscope
• How machine learning algorithms efficiently segment out desired cellular features into three dimensional masks for brain-wide cell counts of neuronal, monocyte, and microglial activity across hundreds of identified areas
• Adaptation of a statistical framework from RNA sequencing for analysis of these large datasets