Electrophysiology provides a direct readout of neuronal activity at a temporal precision
only limited by the sampling rate. However, interrogating deep brain structures, implanting
multiple targets or aiming at unusual angles still poses significant challenges for
operators, and errors are only discovered by post-hoc histological reconstruction.
Here, we propose a method combining the high-resolution information about bone landmarks
provided by micro-CT scanning with the soft tissue contrast of the MRI, which allowed
us to precisely localize electrodes and optic fibers in mice in vivo. This enables
arbitrating the success of implantation directly after surgery with a precision comparable
to gold standard histology. Adjustment of the recording depth with micro-drives or
early termination of unsuccessful experiments saves many working hours, and fast 3-dimensional
feedback helps surgeons avoid systematic errors. Increased aiming precision enables
more precise targeting of small or deep brain nuclei and multiple targeting of specific
cortical or hippocampal layers.
