Electron and Light Microscopy imaging can now deliver high-quality image stacks of neural structures. However, the amount of human annotation effort required to analyze them remains a major bottleneck. While Machine Learning algorithms can be used to help automate this process, they require training data, which is time-consuming to obtain manually, especially in image stacks. Furthermore, due to changing experimental conditions, successive stacks often exhibit differences that are severe enough to make it difficult to use a classifier trained for a specific one on another. This means that this tedious annotation process has to be repeated for each new stack. In this paper we present a domain adaptation algorithm that addresses this issue by effectively leveraging labeled examples across different acquisitions and significantly reducing the annotation requirements. Our approach can handle complex, non-linear image feature transformations and scales to large microscopy datasets that often involve high-dimensional feature spaces and large 3D data volumes. We evaluate our approach on four challenging Electron and Light Microscopy applications that exhibit very different image modalities and where annotation is very costly. Across all applications we achieve a significant improvement over the state-of-the-art Machine Learning methods and demonstrate our ability to greatly reduce human annotation effort.