Non-uniform olivocerebellar conduction time in the vermis of the rat cerebellum

Abstract

It has been proposed that the conduction velocities of cerebellar climbing fibre (olivocerebellar) axons are tuned according to length, in order to precisely fix the conduction time between the inferior olive and cerebellar cortex. Some data conflict with this view. We have re-evaluated this issue using the climbing fibre reflex. The white matter of the tip of one folium in lobule VI or VII was stimulated electrically 0.5-1 mm below the surface and recordings were made from Purkinje cells in lobules VIII and IX. Reflex evoked climbing fibre (CF) responses (33 units) were recorded at different depths from Purkinje cells found in a narrow sagittal zone of cortex as complex spikes. The responses had latencies ranging from 4.3 ms to 11.3 ms. A consistent trend was that Purkinje cell responses recorded at greater depth had shorter CF reflex latencies than those recorded more superficially, both in individual experiments and in grouped data. These data show that the CF reflex latency is not constant, but is directly proportional to the distance an action potential has to travel along a CF. These data are not consistent with tuning of CF conduction velocities to normalize olivocerebellar conduction time, but are consistent with a CF conduction velocity in the cortex of approximately 0.6 m s-1. This suggests that climbing fibres projecting to different parts of the cerebellar cortex may have differences in spike conduction time of a few milliseconds, and that submillisecond precision is not an important element of the climbing fibre signal.

Figure 1. A schematic representation of the experimental arrangement

The drawing shows two cerebellar folia innervated by inferior olivary neurones that are coupled via gap junctions. A stimulating electrode in the cerebellar lobule on the left will antidromically activate some olivary neurones which, through electrical coupling, produces orthodromic activity in the CF projections to the folium on the right. If the olivocerebellar conduction time is tuned to compensate for conduction distance, then the reflex activation of Purkinje cells should occur at a similar time, regardless of the location of the Purkinje cell (e.g. the time taken for an action potential to travel the distance (AD +x) to a deep Purkinje cell should be same as the time taken to travel the distance (AD +x+y) to a superficially located Purkinje cell). If the olivocerebellar conduction time is not tuned to compensate for conduction distance, then the reflex activation of Purkinje cells should not depend on depth.

Figure 2. Extracellular Purkinje cell complex spike responses evoked via the climbing fibre reflex

Climbing fibre reflex responses recorded from a Purkinje cell (2.02 mm deep). Stimulation of a more rostral folium (130 μA) evoked CF responses at a minimal latency of 8.4 ms. As previously described, these show some jitter in latency and sometimes fail (lowermost trace). The climbing fibre responses show a complex form, and can be compared to the simple spikes of the same neurone (arrows).

Figure 3. Depth–latency relationships: single penetration data

This shows data from experiments in which more than one Purkinje cell with CF reflex activation from a single stimulus site could be recorded in one electrode penetration. In two tracks three cells could be recorded, the relative positions of the stimulating electrode (filled circle) and the entry point of the recording electrode (unfilled circle) are shown on the diagrams to the left. The plot on the right shows the relationship between latencies of the CF reflexes and recording depths for these tracks (filled diamonds and filled circles), as well as data from 3 other penetrations in which 2 Purkinje cells were found (filled squares).

Figure 4. Depth-latency relationships: grouped data

The scatterplot shows latencies of CF reflex responses against depth of recording. There is a significant relationship: the depth of the recorded unit was significantly predictive of the latency of the recorded unit (t statistic, P < 0.001; F= 31.2, P < 0.001). Least squares regression analysis revealed an inverse relationship (y= 8.635 − 1.724x). The continuous line through the data points represents the least squares regression; the dashed lines delimit the prediction interval and the dotted lines the 95% confidence interval (n= 33). These data were obtained from 11 different experiments, which may explain some of the variation in latency at each depth.