What are Stereotaxic Devices?

Finding and targeting a small brain area reliably and precisely in a live animal or human is not an easy task. The brain is not one uniform organ but rather has many subdivisions that perform different roles. There are brain areas that help us see, hear, or smell, areas that control muscle movement, areas that help us think complex thoughts, and many others. Most of these areas are very small – in a rat or mouse, for example, they can be just fractions of a millimeter. They can also be buried deep inside the brain and under multiple other brain areas which perform entirely different functions. Targeting a particular area of interest with a tool such as an electrode, an injection pipette, or an optical fiber therefore requires a very high level of precision. For some interventions, if the tool is off by only one degree, it will miss the target brain area entirely. Missing the intended target could mean that the tool is now placed in an entirely different brain area which performs an entirely different function than the one that was intended.

Stereotaxic devices are tools that aid in the accurate targeting of brain areas. The most commonly used procedure by stereotaxic devices makes use of established correlations between landmarks on the outer skull (such as bone sutures) and the location of brain areas inside the skull. The two most used landmarks on top of the skull are called Bregma and Lambda. When performing a typical neurosurgical procedure, an investigator uses a stereotaxic apparatus that holds the animal’s head securely in place. Bregma and Lambda are surgically exposed and brought into the same horizontal plane to accomplish “skull-flat”. In many cases, this also includes the leveling of the skull medio-laterally axis. Practically, skull-flat is accomplished by measuring the z-coordinates of Bregma and Lambda (often manually), followed by (manual) adjustments with a manipulator. Multiple iterations of measuring and adjusting are needed for an acceptable level of precision. The target brain area is then described relative to skull-flat, for example, “rotate by x degrees, drill there, and advance the tool by xx micrometers”.

Challenges with Traditional Stereotaxic Devices

Challenges with this traditional approach include that these manual adjustments take a significant amount of time, which is costly in terms of the animal’s time under anesthesia, which in turn affects the mortality of the procedure. Also, many devices operate purely mechanically and require the manual movement of manipulators, introducing jitter, friction, and inertia, and thus, a perfect skull-flat position is very difficult to accomplish. Next, after skull-flat is accomplished, the coordinates of the target brain area need to be known, thus there needs to be a history of targeting that exact brain area in that species/age group/strain. If none exists, which is the case for the majority of species and age groups, coordinates need to be determined via pilot studies. Finally, even if atlas systems and coordinates are available, methods to translate a given location from the virtual coordinate system of the atlas into the corresponding coordinate in the live brain are rudimentary. While this lack of sophisticated technology may be acceptable for some stereotactically simple types of interventions (for example, targeting large cortical areas with a dorsal approach), it is not acceptable for many other experiments that target small and deep brain areas which can have a significant failure rate. Even in cases where a lab has the expertise to target the desired brain area with a relatively high success rate (for example, because they employ a very skilled lab member), this is problematic since the success depends on that person and their “magic touch” – effectively reducing the reproducibility of these experiments for all other labs that don’t have access to that person. Even the same lab may have trouble reproducing their own experiments once that person leaves.

How Can PopNeuron’s StereoAim ST4000 Help Overcome These Challenges?

PopNeuron’s ST4000 stereotaxic device is a high-end and semi-automated device for small animal use which addresses many of the weaknesses with competitor’s devices and solves many of the challenges described above. The device is based on a hexapod (Stewart platform) at its core. The hexapod is compatible with multiple attachments to securely position the animal’s skull (ear bars, bite bars, head posts) and has an integrated heat pad. The six axes allow for stable and precise positioning of the animal and automated skull flat. A 3D reconstruction algorithm analyzes the skull and skull position with hundreds of landmarks and calculates the position of the reconstructed skull relative to skull flat – and subsequently executes movements of the hexapod to move the animal into skull flat position. Thus, skull flat is accomplished automatically within just a few seconds and is based on the analysis of not one or two landmarks, but hundreds of points.