Activity of Cerebellar Nuclei Neurons Correlates with ZebrinII Identity of Their Purkinje Cell Afferents

Abstract

Purkinje cells (PCs) in the cerebellar cortex can be divided into at least two main subpopulations: one subpopulation that prominently expresses ZebrinII (Z+), and shows a relatively low simple spike firing rate, and another that hardly expresses ZebrinII (Z–) and shows higher baseline firing rates. Likewise, the complex spike responses of PCs, which are evoked by climbing fiber inputs and thus reflect the activity of the inferior olive (IO), show the same dichotomy. However, it is not known whether the target neurons of PCs in the cerebellar nuclei (CN) maintain this bimodal distribution. Electrophysiological recordings in awake adult mice show that the rate of action potential firing of CN neurons that receive input from Z+ PCs was consistently lower than that of CN neurons innervated by Z– PCs. Similar in vivo recordings in juvenile and adolescent mice indicated that the firing frequency of CN neurons correlates to the ZebrinII identity of the PC afferents in adult, but not postnatal stages. Finally, the spontaneous action potential firing pattern of adult CN neurons recorded in vitro revealed no significant differences in intrinsic pacemaking activity between ZebrinII identities. Our findings indicate that all three main components of the olivocerebellar loop, i.e., PCs, IO neurons and CN neurons, operate at a higher rate in the Z– modules.

Cerebellum Involvement in Dystonia During Associative Motor Learning: Insights From a Data-Driven Spiking Network Model

“…This PC burst-firing contributed to abnormal burst-firing patterns of DCN, which showed pauses during increased PC activity as well as increased firing during PC pauses. Thus, the irregularity of PC and DCN neurons was significantly higher than in the healthy network; PC baseline activity was similar and DCN baseline was slightly different from the control condition ( Supplementary Figure 5 ), but still in the physiological ranges reported for the activity of DCN in EBCC-related cerebellar modules ( de Zeeuw and Ten Brinke, 2015 ; Beekhof et al, 2021 ).…”

“…Moreover, due to the altered PC firing, DCN also exhibited a corresponding burst-firing pattern and increased irregularity ( Supplementary Figure 5 ). Baseline firing rates were statistically different from the control condition, but still in the physiological ranges for the activity of PCs and DCN of EBCC-related cerebellar modules ( de Zeeuw and Ten Brinke, 2015 ; Beekhof et al, 2021 ).…”

Molecular Identity and Location Influence Purkinje Cell Vulnerability in Autosomal-Recessive Spastic Ataxia of Charlevoix-Saguenay Mice

“…Purkinje cell projections to the CN are not randomly organized, but cluster into different zones with different molecular profiles ( Chung et al, 2009 ), and CN neurons receiving input from predominantly zebrin-negative Purkinje cells fire at higher frequencies in vivo than those that receive input predominantly from zebrin-positive Purkinje cells. Therefore, the preferential loss of either zebrin-negative or -positive innervation of the CN likely leads to a drastic alteration in the output of the cerebellar circuit ( Beekhof et al, 2021 ). Notably, there is very little zebrin-positive innervation in the anterior portions of the nuclei ( Hawkes and Leclerc, 1986 ; Sugihara, 2011 ).…”

Influence of data sampling methods on the representation of neural spiking activity in vivo

“… 37 , 38 , 39 Purkinje cell firing rate and pattern are distinct between at least two populations, 1 , 2 , 40 , 41 which are consistent with zebrinII molecular expression and specific pre- and post-synaptic partners. 42 , 43 , 44 The modular organization further influences the firing activity of the cerebellar nuclei projection neurons, 45 which are classified as excitatory and inhibitory neurons, each with their specific synaptic partners 46 and electrophysiological properties. 3 , 47 , 48 It is difficult to distinguish between the subtypes of Purkinje cells and nuclei neurons during standard in vivo recordings in the cerebellum because the different populations only partially follow anatomical boundaries within the cerebellar cortex and nuclei.…”

“…Additionally, even though the mean firing rate and pattern are different, the range of these parameters overlaps between molecularly distinct subtypes of Purkinje cells and nuclei neurons. 3 , 45 , 49 Therefore, the diversity of firing properties within whole populations of Purkinje cells and nuclei neurons represents intercellular variability, provided by the heterogeneity of intrinsic properties and synaptic inputs, plus intracellular variability, provided by the dynamic impact of the many sensorimotor signals. Thus, the complexity and dynamics of cerebellar function offer an inroad to explore data sampling in both diverse and uniform contexts.…”