Spontaneous cluster activity in the inferior olivary nucleus in brainstem slices from postnatal mice

Understanding the human brain remains one of the greatest challenges facing the modern scientific community. With over one trillion neurons making up the organ, grasping the vast complexity and interconnectivity of the brain is no small task. One of the major aspects of brain function that is still under study is its development. Significant advances have been made in understanding how the brain works once it is fully functioning, but there is still a need for research to understand how the brain gets to its developed state. For example, it is widely known that the cerebellum is organized into modules, but the significance and origin of this state is still a mystery to the scientific community. Some behavioral studies have pointed to these modules as being the source of motor activity, but results from this research remain inconclusive. As such, Rekling, Jensen, and Jahnsen from Copenhagen University—Panum Institute have devised a study to try and tackle this mystery and uncover yet another layer of the brain's story. To do this, they looked at the smallest modules made up of IO neurons and climbing fibers that connect to the cerebellum through Purkinje cells. Specifically, they wanted to try and determine when these neurons form so that they could begin to understand what role they play in the functioning of the brain and, specifically, the cerebellum.

One of the key focuses of this study was on the formation of gap junctions between IO neurons largely due to the important role these play in proper development of cerebral modules. Understanding these gap junctions is critical to understanding important aspects dealing with the development of motor control. A key method for examining this phenomenon was calcium imaging. By using the Fluo-8 AM Ca²⁺ indicator, researchers were able to obtain vivid and robust snapshots of intracellular activity within the brain. Because Fluo-8 AM is said to be at least twice as bright as other indicators, seeing results and tracking the movements of Ca²⁺ can be done much more effectively, which helps to boost the validity of the results obtained in the study.

After studying the spatiotemporal activity patterns of IO neurons and within an in vitro brain slice, researchers in this study were able to determine that IO neurons spontaneously generate clusters of neurons that are co-active in motor activity. This indicates the possible beginning of the formation of these modules that are so critical to motor activity and helps push the threshold of understanding for this part of the brain. The role of calcium imaging in this study cannot be understated; since Fluo-8 AM can be easily loaded and is not temperature dependent, researchers can be sure that the results they receive from the indicator are accurate. Having this kind of trust in the instruments used during a study like this is vital for obtaining reliable results.

References

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1. Rekling, Jens C., Kristian HR Jensen, and Henrik Jahnsen. "Spontaneous cluster activity in the inferior olivary nucleus in brainstem slices from postnatal mice." The Journal of physiology 590.7 (2012): 1547-1562.