We want to understand the function of the cerebellum. It makes every movement as fast, accurate, and consistent as possible but no one understands yet exactly how it does this. Optimizing movements is probably important for survival since the cerebellum represents a large investment of brain resources. It contains roughly twice as many neurons as the entire cerebral cortex.
We could use any movement to study the cerebellum but currently we use voluntary rapid eye movements, called saccades. These movements offer several advantages. For example, the saccade-related parts of the cerebellum are much better described than other areas, we can measure saccades very accurately, and saccades involve only six extraocular muscles so their organization is easier to characterize than, say, a limb movement. Every part of the cerebellum is nearly identical so we expect that what we learn about saccades will help us understand the cerebellum's role in all movements.
01-OMV-CFN projThe cerebellum does two jobs. It affects each movement immediately by contributing to every motor commands with a signal that makes movements fast, accurate, and consistent. Over a longer period it alters its contribution to motor commands so that movements remain accurate when growth , aging, or injury render previous commands inaccurate. For example, why do limb movements remain accurate during childhood when the limb length, weight, and strength change significantly and more or less continuously? This sustained accuracy is not simply a consequence of a the limb becoming stronger at exactly the same rate that it is becoming heavier . The cerebellum monitors movement accuracy and compensates when movements become inaccurate for any reason.
We study how the cerebellum does both jobs. To understand its immediate effect on movements, we record from neurons in the cerebellum as the monkey makes saccades and we measure saccades after small lesions in the cerebellum. We use these data to work out how the cerebellum processes the signals that it receives into the output that makes saccades fast, accurate, and consistent. We recently found that the cerebellum sends incoming signals through slowly-conducting fibers that act as delay lines to provide the proper timing of saccade deceleration.
To understand how the cerebellum keeps saccades accurate in the long term we elicit changes in cerebellar output by making saccades seem to be inaccurate. We do this by manipulating the visual target that the monkey tracks with its eye movements. We record from neurons as the cerebellum compensates for this apparent inaccuracy and we temporarily turn off small parts of the cerebellum with drugs. With these data we work out where in the cerebellum compensation occurs. We have found that it occurs in the cerebellar cortex, and not the cerebellar nuclei.
We also use neuroanatomical tracing to learn how different parts of the cerebellum connect to each other and to the rest of the brain.02-95 day monk cbl The top panel in Figure 1 shows the positions of the saccade-related part of the cerebellar cortex and the medial cerebellar nucleus. the bottom two panels show an injection of tracer into saccade-related cerebellar cortex and the resultant labeling of the projection to the saccade-related part of the medial cerebellar nucleus.
Finally, we have begun using immunohistochemistry to examine the development of the cerebellum Figure 2 shows a section from the cerebellum of a developing monkey fetus 95 days after conceptio. In this section different types of cerebellar neurons are labeled with different colors.
Together, these different techniques are starting to provide the components of a coherent and detailed description of how the cerebellum functions.
Publications [from PubMed]
- Distribution of N-Acetylgalactosamine-Positive Perineuronal Nets in the Macaque Brain: Anatomy and Implications.Mueller AL, Davis A, Sovich S, Carlson SS, Robinson FRNeural plasticity. 2016 ; 2016 : 6021428
- N-acetylgalactosamine positive perineuronal nets in the saccade-related-part of the cerebellar fastigial nucleus do not maintain saccade gain.Mueller A, Davis A, Carlson SS, Robinson FRPloS one. 2014 ; 9 3: e86154
- Buzunov E, Mueller A, Straube A, Robinson FRBrain research. 2013 Mar; 1503 : 33-42
- Mueller AL, Davis AJ, Robinson FRNeuroscience. 2012 Nov; 224 : 38-47