What Is Stereotaxic Surgery in Mice?

Stereotaxic surgery is a minimally invasive procedure that allows researchers to access specific locations deep within the brain using a three-dimensional coordinate system. This technique is a standard method in neuroscience for precisely targeting structures that cannot be located by sight. It is commonly performed on animal models, particularly mice, to investigate the brain’s complex functions. The procedure enables experimental manipulations, from delivering substances directly into the brain to implanting devices for monitoring or stimulating neural activity.

Purpose of Stereotaxic Surgery in Mice

The fundamental purpose of this surgical technique is to introduce instruments or substances to a precise, predetermined location within the brain. This high degree of accuracy is necessary for a variety of experimental goals, such as manipulating genes, observing the effects of drugs on neural circuits, or measuring neurotransmitters.

Mice are frequently used for these studies because their genetics are well understood and easily manipulated, allowing for the creation of transgenic models that mimic human neurological and psychiatric disorders. The mouse brain’s anatomy has been extensively mapped, and its relatively small size makes it manageable for this type of precise surgical work. The shorter lifespan and cost-effectiveness of mice also allow for more extensive and rapid testing of new theories and potential treatments.

The Stereotaxic Surgical Process

The procedure begins with the mouse under general anesthesia, with its body temperature maintained by a heating pad. The animal’s head is then secured in a stereotaxic frame, which immobilizes it and provides a stable, three-dimensional grid for navigation.

With the head fixed, the surgeon uses a brain atlas, a detailed map of the mouse brain, to determine the target coordinates. These are calculated relative to visible landmarks on the skull, like bregma and lambda, where skull bones intersect. This system allows the surgeon to calculate the precise anterior-posterior, medial-lateral, and dorsal-ventral coordinates needed to reach any deep brain structure. This ensures that targeting is consistent and reproducible across different animals.

Once the coordinates are set on the frame’s manipulators, the surgeon makes a small incision in the scalp to expose the skull. A tiny hole, called a burr hole, is drilled at the calculated position. Through this opening, a fine instrument like a cannula or electrode is slowly lowered to the predetermined depth, with placement accuracy at the micrometer level to minimize damage.

After the injection or implantation is complete, the instrument is withdrawn, and the incision is closed with sutures or surgical clips. The mouse is then removed from the anesthetic and placed in a clean, warm environment to recover. This process ensures the experimental manipulation is confined to the intended brain region, which is necessary for interpreting the research results.

Research Applications and Discoveries

Stereotaxic surgery in mice is used to map neural circuits that control behaviors like learning, memory, fear, and motivation. By implanting optical fibers, researchers can use optogenetics to activate or inhibit specific neurons. This allows them to observe the direct effect on an animal’s behavior, providing evidence for a neural pathway’s function.

This method has advanced the understanding of neurological and psychiatric disorders. In Parkinson’s disease research, surgery is used to deliver neurotoxins to specific brain regions in mice, creating a model that mimics the cell loss in human patients. Scientists can then test therapies, such as new drugs or gene therapies, in these models. The technique is also applied to study Alzheimer’s disease, epilepsy, addiction, and depression.

The surgery’s precision enables testing advanced therapeutic interventions like Deep Brain Stimulation (DBS), a treatment for Parkinson’s disease. Mouse models allow researchers to explore how DBS works, optimize parameters, and identify new targets. The targeted delivery of viral vectors for gene therapy can also be tested for safety and effectiveness before clinical trials.

Animal Welfare and Ethical Considerations

The well-being of animals used in research is governed by strict ethical guidelines, with a focus on managing pain and distress. The surgery is performed under full anesthesia, and the animal’s vital signs are monitored to ensure it remains stable and unconscious.

Post-operative care is also a priority. Following the surgery, mice receive analgesics, or pain-relieving medications, to minimize discomfort during recovery. They are closely monitored for any signs of infection or distress and are provided with easily accessible food and water to support their healing process.

All research involving animal surgery must be approved by an oversight body like an Institutional Animal Care and Use Committee (IACUC). These committees ensure the research is justified and that methods are as humane as possible. They operate on the principles of the “3Rs”:

• Replacement: Using non-animal methods whenever possible.
• Reduction: Using the minimum number of animals necessary.
• Refinement: Modifying procedures to minimize any potential pain or distress.