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Modulation of Purkinje cell complex spike waveform by synchrony levels in the olivocerebellar system.

Lang EJ, Tang T, Suh CY, Xiao J, Kotsurovskyy Y, Blenkinsop TA, Marshall SP, Sugihara I - Front Syst Neurosci (2014)

Bottom Line: Control experiments showed that changes in variance with synchrony were primarily due to changes in the CS waveform, as opposed to changes in the strength of field potentials from surrounding cells.Direct counts of spikelets showed that their number increased with synchronization of CS activity.In sum, these results provide evidence of a causal link between two of the distinguishing characteristics of the olivocerebellar system, its ability to generate synchronous activity and the waveform of the CS.

View Article: PubMed Central - PubMed

Affiliation: Department of Neuroscience and Physiology, New York University School of Medicine New York, NY, USA.

ABSTRACT
Purkinje cells (PCs) generate complex spikes (CSs) when activated by the olivocerebellar system. Unlike most spikes, the CS waveform is highly variable, with the number, amplitude, and timing of the spikelets that comprise it varying with each occurrence. This variability suggests that CS waveform could be an important control parameter of olivocerebellar activity. The origin of this variation is not well known. Thus, we obtained extracellular recordings of CSs to investigate the possibility that the electrical coupling state of the inferior olive (IO) affects the CS waveform. Using multielectrode recordings from arrays of PCs we showed that the variance in the recording signal during the period when the spikelets occur is correlated with CS synchrony levels in local groups of PCs. The correlation was demonstrated under both ketamine and urethane, indicating that it is robust. Moreover, climbing fiber reflex evoked CSs showed an analogous positive correlation between spikelet-related variance and the number of cells that responded to a stimulus. Intra-IO injections of GABA-A receptor antagonists or the gap junction blocker carbenoxolone produced correlated changes in the variance and synchrony levels, indicating the presence of a causal relationship. Control experiments showed that changes in variance with synchrony were primarily due to changes in the CS waveform, as opposed to changes in the strength of field potentials from surrounding cells. Direct counts of spikelets showed that their number increased with synchronization of CS activity. In sum, these results provide evidence of a causal link between two of the distinguishing characteristics of the olivocerebellar system, its ability to generate synchronous activity and the waveform of the CS.

No MeSH data available.


Related in: MedlinePlus

Relationship between spikelet-related variance and CS synchrony holds under urethane anesthesia. (A) Bubble plot representing the synchrony distribution with respect to cell M. The relative positions of the recorded PCs in the array are indicated by circles, and the encircled “M.” The areas of the circles are proportional to the synchrony between CSs of cell M and the other PCs in the array. Note that cell M's activity is strongly correlated mainly with neighboring cells. Black circles along with cell M comprise the cell group that was analyzed. (B) Plots of average variances during the CSs and the baseline periods as a function of CS synchrony among group members. Top graph is for cell M. Bottom graph is for another group member (indicated by black circle in third row, second column of the array). Regression lines are fits to the entire set of CSs for each cell, not the average points that are plotted. Error bars are one SD. Synchrony defined using a 5 ms bin. (C) Distribution of correlation values for the relationship between synchrony and variance for spikelet-related and baseline periods. Circles indicate individual cell r values, horizontal lines show distribution means, and error bars indicate the SD.
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Figure 5: Relationship between spikelet-related variance and CS synchrony holds under urethane anesthesia. (A) Bubble plot representing the synchrony distribution with respect to cell M. The relative positions of the recorded PCs in the array are indicated by circles, and the encircled “M.” The areas of the circles are proportional to the synchrony between CSs of cell M and the other PCs in the array. Note that cell M's activity is strongly correlated mainly with neighboring cells. Black circles along with cell M comprise the cell group that was analyzed. (B) Plots of average variances during the CSs and the baseline periods as a function of CS synchrony among group members. Top graph is for cell M. Bottom graph is for another group member (indicated by black circle in third row, second column of the array). Regression lines are fits to the entire set of CSs for each cell, not the average points that are plotted. Error bars are one SD. Synchrony defined using a 5 ms bin. (C) Distribution of correlation values for the relationship between synchrony and variance for spikelet-related and baseline periods. Circles indicate individual cell r values, horizontal lines show distribution means, and error bars indicate the SD.

Mentions: The above results demonstrating a correlation between spikelet-related variance and CS synchrony were all obtained in ketamine/xylazine anesthetized animals. To rule out the possibility that this relationship is specific to the ketamine/xylazine state, we analyzed data from urethane anesthetized animals (n = 21 PCs, 2 animals). Multielectrode recordings of spontaneous CS activity were obtained for 20-min periods. In these experiments we did not have zebrin stained tissue or simultaneous recordings of cerebellar nuclear cells, and so cell groups were formed as a localized cluster of PCs that had synchronized CS activity. The spatial distribution of synchrony under urethane is similar to that found under ketamine; that is, synchronous activity is most common among PCs aligned in the same rostrocaudal strip of cortex (Blenkinsop and Lang, unpublished results), and this rostrocaudal pattern aligns with the zebrin banding and PC-nuclear cell projection patterns (Sugihara et al., 2007; Sugihara, 2011). Therefore, these groups should be quite similar to those formed by the other two criteria. An example of the synchrony distribution with respect to one cell (cell M) of the recording array is shown in the bubble plot of Figure 5A, where the area of each circle represents the synchrony between the CSs of cell M and those of the PC at the location of the circle. Because synchrony levels in the urethane experiments were somewhat lower than those in the ketamine ones, a 5-ms window was used to define synchrony in order to obtain enough synchronous events that included a large percentage of PCs in the group.


Modulation of Purkinje cell complex spike waveform by synchrony levels in the olivocerebellar system.

Lang EJ, Tang T, Suh CY, Xiao J, Kotsurovskyy Y, Blenkinsop TA, Marshall SP, Sugihara I - Front Syst Neurosci (2014)

Relationship between spikelet-related variance and CS synchrony holds under urethane anesthesia. (A) Bubble plot representing the synchrony distribution with respect to cell M. The relative positions of the recorded PCs in the array are indicated by circles, and the encircled “M.” The areas of the circles are proportional to the synchrony between CSs of cell M and the other PCs in the array. Note that cell M's activity is strongly correlated mainly with neighboring cells. Black circles along with cell M comprise the cell group that was analyzed. (B) Plots of average variances during the CSs and the baseline periods as a function of CS synchrony among group members. Top graph is for cell M. Bottom graph is for another group member (indicated by black circle in third row, second column of the array). Regression lines are fits to the entire set of CSs for each cell, not the average points that are plotted. Error bars are one SD. Synchrony defined using a 5 ms bin. (C) Distribution of correlation values for the relationship between synchrony and variance for spikelet-related and baseline periods. Circles indicate individual cell r values, horizontal lines show distribution means, and error bars indicate the SD.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
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Figure 5: Relationship between spikelet-related variance and CS synchrony holds under urethane anesthesia. (A) Bubble plot representing the synchrony distribution with respect to cell M. The relative positions of the recorded PCs in the array are indicated by circles, and the encircled “M.” The areas of the circles are proportional to the synchrony between CSs of cell M and the other PCs in the array. Note that cell M's activity is strongly correlated mainly with neighboring cells. Black circles along with cell M comprise the cell group that was analyzed. (B) Plots of average variances during the CSs and the baseline periods as a function of CS synchrony among group members. Top graph is for cell M. Bottom graph is for another group member (indicated by black circle in third row, second column of the array). Regression lines are fits to the entire set of CSs for each cell, not the average points that are plotted. Error bars are one SD. Synchrony defined using a 5 ms bin. (C) Distribution of correlation values for the relationship between synchrony and variance for spikelet-related and baseline periods. Circles indicate individual cell r values, horizontal lines show distribution means, and error bars indicate the SD.
Mentions: The above results demonstrating a correlation between spikelet-related variance and CS synchrony were all obtained in ketamine/xylazine anesthetized animals. To rule out the possibility that this relationship is specific to the ketamine/xylazine state, we analyzed data from urethane anesthetized animals (n = 21 PCs, 2 animals). Multielectrode recordings of spontaneous CS activity were obtained for 20-min periods. In these experiments we did not have zebrin stained tissue or simultaneous recordings of cerebellar nuclear cells, and so cell groups were formed as a localized cluster of PCs that had synchronized CS activity. The spatial distribution of synchrony under urethane is similar to that found under ketamine; that is, synchronous activity is most common among PCs aligned in the same rostrocaudal strip of cortex (Blenkinsop and Lang, unpublished results), and this rostrocaudal pattern aligns with the zebrin banding and PC-nuclear cell projection patterns (Sugihara et al., 2007; Sugihara, 2011). Therefore, these groups should be quite similar to those formed by the other two criteria. An example of the synchrony distribution with respect to one cell (cell M) of the recording array is shown in the bubble plot of Figure 5A, where the area of each circle represents the synchrony between the CSs of cell M and those of the PC at the location of the circle. Because synchrony levels in the urethane experiments were somewhat lower than those in the ketamine ones, a 5-ms window was used to define synchrony in order to obtain enough synchronous events that included a large percentage of PCs in the group.

Bottom Line: Control experiments showed that changes in variance with synchrony were primarily due to changes in the CS waveform, as opposed to changes in the strength of field potentials from surrounding cells.Direct counts of spikelets showed that their number increased with synchronization of CS activity.In sum, these results provide evidence of a causal link between two of the distinguishing characteristics of the olivocerebellar system, its ability to generate synchronous activity and the waveform of the CS.

View Article: PubMed Central - PubMed

Affiliation: Department of Neuroscience and Physiology, New York University School of Medicine New York, NY, USA.

ABSTRACT
Purkinje cells (PCs) generate complex spikes (CSs) when activated by the olivocerebellar system. Unlike most spikes, the CS waveform is highly variable, with the number, amplitude, and timing of the spikelets that comprise it varying with each occurrence. This variability suggests that CS waveform could be an important control parameter of olivocerebellar activity. The origin of this variation is not well known. Thus, we obtained extracellular recordings of CSs to investigate the possibility that the electrical coupling state of the inferior olive (IO) affects the CS waveform. Using multielectrode recordings from arrays of PCs we showed that the variance in the recording signal during the period when the spikelets occur is correlated with CS synchrony levels in local groups of PCs. The correlation was demonstrated under both ketamine and urethane, indicating that it is robust. Moreover, climbing fiber reflex evoked CSs showed an analogous positive correlation between spikelet-related variance and the number of cells that responded to a stimulus. Intra-IO injections of GABA-A receptor antagonists or the gap junction blocker carbenoxolone produced correlated changes in the variance and synchrony levels, indicating the presence of a causal relationship. Control experiments showed that changes in variance with synchrony were primarily due to changes in the CS waveform, as opposed to changes in the strength of field potentials from surrounding cells. Direct counts of spikelets showed that their number increased with synchronization of CS activity. In sum, these results provide evidence of a causal link between two of the distinguishing characteristics of the olivocerebellar system, its ability to generate synchronous activity and the waveform of the CS.

No MeSH data available.


Related in: MedlinePlus