Purkinje cells

…Early postnatally, cerebellar Purkinje cells (PC) are connected by multiple climbing fibers (CF) emerging from the inferior olive in th

Bergmann glia (BG) are radial glial cells in the cerebellar cortex that have multiple functions. They have been shown to interact with Purkinje cells in several ways: they modulate synaptic inputs to Purkinje cells, regulate excitability through external potassium concentration, and directly affect Purkinje cells through neurotransmitter release. In this study, we genetically expressed hM3Dq in BGs through GFAP-promoter-contained AAV virus. We showed that this BG-PC regulation is mediated by the NMDA receptor and GABAA receptor. Furthermore, using calcium imaging, we confirmed that BG activati

…Purkinje cells, the sole output neurons of the cerebellar cortex, are often involved in the underlying pathology, but their specific functions during locomotor control in health and disease remain obfuscated. We aimed to describe the effect of gradual adult-onset Purkinje cell degeneration on gaiting patterns in mice, and to determine whether two different mechanisms that both lead to Purkinje cell degeneration cause different patterns in the development of gait ataxia. Using the ErasmusLadder together

…In particular, while cerebellar Purkinje cell activity is strongly modulated by the locomotor stride cycle, it is not clear how that activity is constructed from its afferent inputs, nor how it can be used for real-time control. To investigate these questions, we are recording cerebellar population activity with Neuropixels probes during locomotion in head-fixed mice, combined with high-speed 3D tracking of lim

The ability to learn and adapt precise motor programs in a changing environment is crucial for animal survival. A prominent theory suggests that the cerebellum utilizes forward models to compare perceived sensory stimuli (perceived reafference) with predictions based on past experiences (expected reafference), quickly adjusting motor programs to environmental changes. Utilizing a new mouse behavioral paradigm involving sensorimotor perturbations in a simple joystick pulling task, we can decipher the role of the cerebellum in rapid motor adaptation. Previous results revealed parasagittal bands

…carrying the information sent by the Purkinje cells from the cerebellar cortex to extra-cerebellar structures. Although circuits recruiting the DCN were shown to modulate multiple motor and nonmotor functions, the mechanisms facilitating excitability and neurotransmission at their projection neurons are poorly understood. Various Transient Receptor Potential (TRP) ion channels were shown to regulate neuronal activity in the cerebellar cortex, whereas the characterization of their functional roles in the DCN

…fiber (CF) input to cerebellar Purkinje cells (PC) acts as a “teacher” signal during motor learning and drives cerebellar plasticity. Although the CF input reliably evokes PC dendritic spikes, it is not the only signal that modulates this post-synaptic response. To disentangle the modulation of the pre-synaptic CF burst from that of its post-synaptic PC dendritic response, we simultaneously imaged PC dendrites and CF terminals with 2-photon mic

…Additionally, glycogen was observed in Purkinje cells (PCs), the principal neurons of the cerebellar c

Climbing fiber inputs to the cerebellar cortex drive low-frequency bursts of activity in Purkinje cells - known as complex spikes - which are thought to encode sensorimotor errors critical for movement refinement. Yet, the precise nature of these signals remains elusive for complex behaviors requiring the coordination of multiple body parts, such as locomotion. To understand the contribution of olivary inputs to the cerebellar cortex in locomotor coordination, we performed calcium imaging from Purkinje cell dendrites in unrestrained mice running on treadmills. Combining miniscope imaging with

…of autophagy-mediated death of Purkinje cells (PC) from two months of age, along with dysregulation of the PI3K/AKT/mTOR signalling pathway responsible for proper axonal myelination. Both situations trigger the onset of an ataxic neuromuscular syndrome characterized by motor control impairments. In response to this disturbance, even before PC death occurs, microglia present in the cerebellum can

…dysfunction and significant loss of Purkinje cells, with subsequent involvement of other brain regions, suggesting a potential disease-spreading mechanism. Our study sheds light on SCA2 pathogenesis by revealing the presence of mutant ATXN2 mRNA within small extracellular vesicles (sEVs). These sEVs demonstrate the ability to transport the mutant mRNA to recipient cells, leading to its translation and the formation of mutant protein aggregates, a neuropathological hallmark of SCA2.Additionally

Spinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph disease (MJD), is a polyglutamine disorder caused by an abnormal trinucleotide (CAG) expansion in the ATXN3 gene, leading to neurodegeneration. This translates into severe impairments across the patient’s body functions, and there are no therapies to halt or slow disease progression. Thus, there is an urgent need to identify novel molecular targets to develop disease-modifying therapies. Previously, it was shown that the loss of the tRNA methyltransferase 2 homolog A (TRMT2A) reduced polyglutamine toxicity and aggregation in SC

Christianson syndrome (CS) is an X-linked monogenic neurodevelopmental/neurodegenerative disorder arising from loss of function mutations in the endosomal pH regulator, Na+, K+/H+ exchanger isoform 6 (NHE6) and is estimated to afflict 1 in 16,000–100,000 people worldwide. In addition to significant limitations in cognitive and adaptive abilities, all affected males have ataxia. Mitochondrial dysfunction is increasingly being recognized as an important factor contributing to the pathogenesis of ataxia. In particular, dysregulated mitochondrial fusion and fission events can now be regarded as pl

…Different Purkinje cell subpopulations based on molecular marker expression have been shown to exhibit differences in baseline physiological properties, developmental timeline and synaptic plasticity. These subpopulations have also been linked to different cerebellar-dependent learned behaviors. In this study, we demonstrate that these subpopulations exhibit unique ph

…via changes in synaptic plasticity of Purkinje cells (PCs), which are the main cortical output. However, whether and how motor learning can influence the actual connectivity of PCs is unknown. To address this question, we use a rabies virus (RABV)-based approach to map structural modifications of PC presynaptic inputs in young (3-month-old) and middle-aged mice (1-year-old). To promote motor skill learn

…protein strongly expressed in Purkinje cells (PCs) of the cerebellum and is known to be involved in the regulation of synapse formation and PC dendritic development. The effects of PKCγ are mediated by phosphorylation of target proteins which regulate cytoskeleton dynamics playing a critical role in dendritic development. However, the interaction of PKCγ with cytosk

…consistently shown that cerebellar Purkinje cell modulation is broadly correlated with the locomotor stride cycle. However, much of the firing rate variability has remained unexplained, and it is not yet clear how Purkinje cell population activity could be read out to control whole-body coordination. Here, we performed cell-attached recordings of Purkinje cell simple spike activity in head-fixed mice locomoting for liquid rewards, toget

…of ER diameter to the dimension of cells and ne

Recent research has extended the role of the neurohormone oxytocin far beyond mating and bonding. Oxytocin now appears as a cornerstone that allows individuals to adapt their group interaction in a flexible, age and context-dependent manner. Accordingly, the central oxytocin system has been studied mainly in regions that belong to the "social brain", but not in the cerebellum - a structure traditionally not considered part of it. Recent data challenged this traditional view by showing that the cerebellum actually contributes to cognitive, emotional, and perceptual brain functions. In addition,

…is conveyed by mossy fibers to granule cells (GC) contacting Purkinje cells (PC) belonging to different modules via their long axons, the parallel fibers (PFs). PFs underlie inter-modular communication, which may be at the core of motor coordination. Therefore, the main goal of our research is to understand how intermodular communication in the cerebellar cortex underlies motor adaptation.Using patterned light photostimulat

…of ataxia disorders is the death of Purkinje Cells where Purkinje Cell cerebellar location can influence their vulnerability. Purkinje Cells express certain molecules in a highly patterned manner across the cerebellum, the most studied being aldolase C/zebrin-II (zebrin), expressed in parasagittal stripes across the cerebellum. We investigated if either type of Purkinje Cell was more vulnerable in CS using immunohistochemistry, looking specifically at motor lobules

DYT1 is an autosomal dominant form of dystonia, linked to a deletion (ΔGAG) in the TOR1A gene. The basal ganglia have been found to play a crucial role in the development of dystonia in the TOR1AΔGAG murine model. Experimental evidence has also indicated that the cerebellar cortex is likely to play a pivotal role in the pathophysiology of this disorder. We investigated cerebellar cortex activity and synaptic plasticity by performing extracellular recordings in acute parasagittal cerebellar slices with a high-density multielectrode array (HD-MEA) that allows to simultaneously record the activit

One of the key feature of the cerebellar computation is its abilities to predict the sensory consequences of motor commands through the cerebro-cerebello-cortical loop. Prediction capabilities of the cerebellum extend to non-motor functions as attested by an extensive bidirectional connectivity between the cerebellum and the medial prefrontal cortex (mPFC). We hypothesize that the cerebellum make predictions based on contextual and goal-directed information enabling better integration in the PFC and an overall increase efficiency in time related actions.Our aim is to understand better the comm

Purkinje cells (PCs) are known to express both GluK1 and GluK4 kainate receptor (KAR) subunits, but the exact role of KARs in synaptic information transfer to PCs is unknown. In this study, we discovered that climbing fiber (CF) to PC synapses contain heteromeric GluK1/GluK4 synaptic KARs. Genetic deletion of Grik4, which encodes for GluK4 subunits, resulted in the lack of synaptic but not extrasynaptic KARs, while deletion of Grik1 (GluK1 subunits) eliminated both synaptic and extrasynaptic KARs. Surprisingly, the absence of synaptic KARs led to a significant reduction in the EPSC component m