The Roles of the Olivocerebellar Pathway in Motor Learning and Motor Control. A Consensus Paper.

For many decades, the predominant view in the cerebellar field has been that the olivocerebellar system's primary function is to induce plasticity in the cerebellar cortex, specifically, at the parallel fiber-Purkinje cell synapse. However, it has also long been proposed that the olivocerebellar system participates directly in motor control by helping to shape ongoing motor commands being issued by the cerebellum. Evidence consistent with both hypotheses exists; however, they are often investigated as mutually exclusive alternatives. In contrast, here, we take the perspective that the olivocerebellar system can contribute to both the motor learning and motor control functions of the cerebellum and might also play a role in development. We then consider the potential problems and benefits of it having multiple functions. Moreover, we discuss how its distinctive characteristics (e.g., low firing rates, synchronization, and variable complex spike waveforms) make it more or less suitable for one or the other of these functions, and why having multiple functions makes sense from an evolutionary perspective. We did not attempt to reach a consensus on the specific role(s) the olivocerebellar system plays in different types of movements, as that will ultimately be determined experimentally; however, collectively, the various contributions highlight the flexibility of the olivocerebellar system, and thereby suggest that it has the potential to act in both the motor learning and motor control functions of the cerebellum.

Bulk loading of calcium indicator dyes to study astrocyte physiology: key limitations and improvements using morphological maps.

Calcium signaling has been studied in astrocyte cell bodies using bulk loading of calcium indicator dyes, and astrocytes are known to display intracellular calcium transients. An assumption in recent data on the neuronal impact of somatic astrocyte calcium transients has been that bulk loading reflects signaling in relevant astrocyte compartments such as processes. We assessed bulk loading using Sholl analysis (Sholl, 1953) of astrocytes loaded with common calcium indicator dyes and compared these data with Sholl analysis of astrocyte morphology. In the CA1 region of the hippocampus from rats, we found that bulk loading of calcium indicator dyes only reports on calcium signals within the soma and in the most proximal processes, leaving ∼90% of the area of an astrocyte and its extensive processes unsampled. By using morphological reconstructions as "maps" after the imaging session, we present simple procedures that remedy these shortfalls and permit reliable detection of calcium transients in distal astrocyte processes. The data thus reveal limitations in the interpretation of astrocyte calcium imaging data gathered with bulk loading and provide refinements to minimize these shortcomings.

Circuit mechanisms underlying motor memory formation in the cerebellum.

The cerebellum stores associative motor memories essential for properly timed movement; however, the mechanisms by which these memories form and are acted upon remain unclear. To determine how cerebellar activity relates to movement and motor learning, we used optogenetics to manipulate spontaneously firing Purkinje neurons (PNs) in mouse simplex lobe. Using high-speed videography and motion tracking, we found that altering PN activity produced rapid forelimb movement. PN inhibition drove movements time-locked to stimulus onset, whereas PN excitation drove delayed movements time-locked to stimulus offset. Pairing either PN inhibition or excitation with sensory stimuli triggered the formation of robust, associative motor memories; however, PN excitation led to learned movements whose timing more closely matched training intervals. These findings implicate inhibition of PNs as a teaching signal, consistent with a model whereby learning leads first to reductions in PN firing that subsequently instruct circuit changes in the cerebellar nucleus.