Project Wonder - The art of science at the Medical College of Wisconsin

Cerebellum Semaphore

What if deciphering a signaling system could help us understand how the brain controls balance, posture and complex movements such as playing a musical instrument? César Martinez, an MD/PhD student at MCW, is conducting research in the department of pharmacology and toxicology focused on the role of a set of biological transmitters and receivers – known as the endocannabinoid system – during the growth and development of the cerebellum, a region of the brain that contributes to the body’s ability to maintain balance and conduct precise, skillful movements.

The endocannabinoid system includes a number of signaling molecules, or endocannabinoids, that connect to and interact with specific cannabinoid protein receptors located in the brain, spinal cord and nerves spread throughout the body. The system also includes enzymes which control the levels of the signaling molecules. The amount of activity within this system influences numerous aspects of cognition and sensation, including appetite, pain and the learning of motor skills.

Studies have demonstrated that changes in endocannabinoid system signaling can affect the level of communication between nerve cells in the cerebellum that is critical to its ability to maintain balance and coordination. Cesar works with a team of researchers under the guidance of Cecilia J. Hillard, PhDG. Frederick Kasten, Jr. Endowed Chair in Parkinson’s Disease Research, professor of pharmacology and toxicology, associate dean for research and director of the Neuroscience Research Center. Together, they also are studying the role of the endocannabinoid system in psychiatric and neurodegenerative diseases such as schizophrenia, addiction and Parkinson’s disease. By better understanding how the endocannabinoid system affects brain development, as well as its role in the functioning of neural circuits, we move closer to developing and testing potential treatments that influence the endocannabinoid system to help patients. Imaging was conducted at the Microscopy Core in the Neuroscience Research Center led by: Suresh Kumar, PhD, associate professor of pathology and laboratory medicine; Christopher Olsen, PhD, associate professor of pharmacology and toxicology; and Garrett Sauber, microscopy technician.

Research: César Martinez
Principal Investigator: Cecilia Hillard, PhD
Animation and Soundtrack: Alex Boyes
Writing: Greg Calhoun

Image description:
Sagittal cryosections from mouse cerebellum at the primary fissure labeled with immunohistochemistry. Calbindin-positive Purkinje neuron cells are shown (magenta) with VGLUT2-positive glutamatergic synaptic inputs (yellow) and DAPI-positive granule cell layer(cyan).

Immunohistochemistry, Confocal Microscopy, Imaris