Electrophysiological Excitability and Parallel Fiber Synaptic Properties of Zebrin-Positive and -Negative Purkinje Cells in Lobule VIII of the Mouse Cerebellar Slice

Abstract

Heterogeneous populations of cerebellar Purkinje cells (PCs) are arranged into separate longitudinal stripes, which have different topographic afferent and efferent axonal connections presumably involved in different functions, and also show different electrophysiological properties in firing pattern and synaptic plasticity. However, whether the differences in molecular expression that define heterogeneous PC populations affect their electrophysiological properties has not been much clarified. Since the expression pattern of many of such molecules, including glutamate transporter EAAT4, replicates that of aldolase C or zebrin II, we recorded from PCs of different “zebrin types” (zebrin-positive = aldolase C-positive = Z+; and Z−) in identified neighboring stripes in vermal lobule VIII, in which Z+ and Z− stripes occupy similar widths, in the Aldoc-Venus mouse cerebellar slice preparation. Regarding basic cellular electrophysiological properties, no significant differences were observed in input resistance or in occurrence probability of types of firing patterns between Z+ and Z− PCs. However, the firing frequency of the tonic firing type was higher in Z− PCs than in Z+ PCs. In the case of parallel fiber (PF)-PC synaptic transmission, no significant differences were observed between Z+ and Z− PCs in interval dependency of paired pulse facilitation or in time course of synaptic current measured without or with the blocker of glutamate receptor desensitization. These results indicate that different expression levels of the molecules that are associated with the zebrin type may affect the intrinsic firing property of PCs but not directly affect the basic electrophysiological properties of PF-PC synaptic transmission significantly in lobule VIII. The results suggest that the zebrin types of PCs in lobule VIII is linked with some intrinsic electrophysiological neuronal characteristics which affect the firing frequency of PCs. However, the results also suggest that the molecular expression differences linked with zebrin types of PCs does not much affect basic electrophysiological properties of PF-PC synaptic transmission in a physiological condition in lobule VIII.

Heterogeneity of intrinsic plasticity in cerebellar Purkinje cells linked with cortical molecular zones

“…The firing duration and maximum firing current were significantly shorter and smaller, respectively, in Z+ PCs than in Z- PCs in both areas ( Figures S1 B and S1D). In the present study, we did not observe significant differences between Z+ and Z- PCs in the input resistance (80.28 ± 13.97 and 76.89 ± 10.55 MΩ, average ± standard deviation, in 31 Z+ and 31 Z- PCs, respectively), or rheobase current (112.90 ± 31.53 and 119.35 ± 33.36 pA), as observed in our previous study in lobule VIII ( Nguyen-Minh et al., 2019 ).…”

“…By eliminating possible effects caused by the differences in lobule-related factors, afferent inputs, and inhibitory interneuron inputs, which were not necessarily eliminated in previous in vivo and in vitro studies, we could focus on different cellular physiological properties between Z+ and Z- PCs. Our initial study in AldocV mice has shown no difference in input resistance, capacitance, or basic properties in PF-PC synaptic transmission between Z+ and Z- PCs in vermal lobule VIII ( Nguyen-Minh et al., 2019 ). However, this study detected some differences in intrinsic excitability between these PCs, which led us to the present study.…”

“…However, these comparative studies of excitability randomly sampled PCs in various lobules and zones ( Xiao et al., 2014 ; Zhou et al., 2014 ) or compared PCs between lobule III and lobule X, which are mainly occupied by Z- zones and Z+ zones, respectively ( Wu et al., 2019 ). So far, few studies ( Malhotra et al., 2021 ; Nguyen-Minh et al., 2019 ) have compared PCs in neighboring Z+ and Z- zones in the same lobule to eliminate possible effects of lobular differences. Furthermore, the intrinsic plasticity of PCs has not been compared between Z+ and Z- PCs.…”

Modular organization of cerebellar climbing fiber inputs during goal-directed behavior

“…Our analyses on the functional clustering of CF signals revealed broad congruence between the boundaries of the functional clusters and those of AldC expression (Figure 2D and Figure 2—figure supplement 1–4), indicating that the AldC profile can be used as an approximate for cerebellar functional modules at both cellular and microzonal resolutions. Previous studies have suggested several functional differences between AldC+ and AldC− PCs: (i) AldC+ PCs have a lower simple spike rate and a higher complex spike rate than AldC− PCs, which are dependent on co-expressing TRPC3 subtypes (Zhou et al, 2014); (ii) coupling between simple spikes and complex spikes is enhanced in AldC+ PCs (Tang et al, 2017); (iii) AldC+ PCs receive enhanced glutamate release by CF inputs when compared with AldC− PCs (Paukert et al, 2010), but show no difference in parallel fiber-PC synapses (Nguyen-Minh et al, 2018); (iv) at the population level, CF inputs to AldC+ and AldC− compartments are separately and precisely synchronized at the cellular resolution (Tsutsumi et al, 2015); and (v) AldC+ and AldC− PCs have been shown to respond differently to optic flow stimulation in the pigeon cerebellum (Graham and Wylie, 2012). In the present study, we found that more AldC+ PCs than AldC− PCs receive motor-related CF inputs (Figure 2F).…”

“…Accumulating evidence suggests functional difference between AldC+ and AldC− PCs. AldC+ PCs receive enhanced glutamate release by CFs (Paukert et al, 2010), but parallel fiber inputs that are similar to those received by AldC− PCs (Nguyen-Minh et al, 2018). AldC+ and AldC− PCs show distinct firing properties and plasticity rules (Zhou et al, 2014), and differ in interaction between simple and complex spikes (Tang et al, 2017).…”