Cerebellar Development and Plasticity: Perspectives for Motor Coordination Strategies, for Motor Skills, and for Therapy

The role of the mammalian cerebellum ranges from motor coordination, sensory-motor integration, motor learning, and timing to nonmotor functions such as cognition. In terms of motor function, the development of the cerebellum is of particular interest because animal studies show that the development of the cerebellar cortical circuitry closely parallels motor coordination. Ultrastructural analysis of the morphological development of the cerebellar circuitry, coupled with the temporal and spatial identification of the neurochemical substrates expressed during development, will help to elucidate their roles in the establishment of the cerebellar circuitry and hence motor activity. Furthermore, the convenience of a number of naturally occurring mouse mutations has allowed a functional dissection of the various cellular elements that make up the cerebellar circuitry. This understanding will also help in the approach to possible therapies of pathologies arising during development because tile cerebellum is especially prone to such perturbation because of its late development

Corticotropin-releasing factor receptor types 1 and 2 are differentially expressed in pre- and post-synaptic elements in the post-natal developing rat cerebellum

Corticotropin-releasing factor (CRF)-like proteins act via two G-protein-coupled receptors (CRF-R1 and CRF-R2) playing important neuromodulatory roles in stress responses and synaptic plasticity. The cerebellar expression of corticotropin-releasing factor-like ligands has been well documented, but their receptor localization has not. This is the first combination of a light microscopic and ultrastructural study to localize corticotropin-releasing factor receptors immunohistologically in the developing rat cerebellum. Both CRF-R1 and CRF-R2 were expressed in climbing fibres from early stages (post-natal day 3) to the adult, but CRF-R2 immmunoreactivity was only prominent throughout the molecular layer in the posterior cerebellar lobules. CRF-R1 immunoreactivity was concentrated in apical regions of Purkinje cell somata and later in primary dendrites exhibiting a diffuse cytoplasmic appearance. In Purkinje cells, CRF-R1 immunoreactivity was never membrane bound post-synaptically in dendritic spines while CRF-R2 immunoreactivity was found on plasmic membranes of Purkinje cells from post-natal day 15 onwards. We conclude that the localization of these receptors in cerebellar afferents implies their pre-synaptic control of the release of corticotropin-releasing factor-like ligands, impacting on the sensory information being transmitted from afferents. Furthermore, the fact that CRF-R2 is membrane bound at synapses, while CRF-R1 is not, suggests that ligands couple to CRF-R2 via synaptic transmission and to CRF-R1 via volume transmission. Finally, the distinct expression profiles of receptors along structural domains of Purkinje cells suggest that the role for these receptors is to modulate afferent inputs

Learning from novice–expert interaction in teachers’ continuing professional development

Novice–expert interaction plays an important role in teacher professional development for Chinese vocational education and training (VET). Both Chinese and international research shows that expert-teachers’ support is associated with the improvement of novice-teachers’ teaching. However, insights into how exactly novice teachers learn with the help of expert teachers are lacking. The learning processes of four novice VET teachers were explored in the context of a professional development project. Data were collected by semi-structured interviews with novice teachers and recordings of novice–expert interactions. A learning model was constructed based on the interconnected model of professional growth. The results showed that novice teachers internalised comments from expert teachers by active reflection and practice. Moreover, this study suggests that teachers’ professional development is a complicated long-term process, and that during their development the support from expert teachers is an important external source for novice-teachers. Expert-teachers’ support not only provides feedback and suggestions for alternative teaching methods, but also encourages and maintains novice-teachers’ learning. The results are discussed in relation to the cultural (Chinese) and educational context (VET) Teaching and Teacher Learning (ICLON

Картографический метод в изучении территориального рекреационного неравенства

This article investigates the link between teachers' appraisal of specific interpersonal situations in classrooms and their more general interpersonal identity standard, which together form their interpersonal role identity. Using semi-structured and video-stimulated interviews, data on teachers' appraisals and interpersonal identity standards were collected and analyzed using appraisal and interpersonal circumplex theory. Results show a variety of interpersonal identity standards, although the majority of the teachers mentions standards focusing on the codes steering and being friendly. The situation “reacting to student positive behavior” evoked most appraisals that confirmed identity standards. For 13 of the 29 teachers, their identity standard matched with their appraisals. In most cases, however, this match was only to some extent (10 teachers) and sometimes not at all (six teachers). The results suggest that teachers can enhance their relationship with students by becoming more aware of the meanings teachers attach to this relationship in specific situations

Achieving professional agency for school development in the context of having a PhD scholarship.: An intricate interplay

In this multiple case study, we investigated teachers professional agency in relation to school development in the context of having a PhD scholarship, and the interplay of personal and social resources. Semi-structured interviews were conducted with 11 Dutch secondary education teachers with PhD scholarships. Teachers are achieving bounded, restricted and extensive agency, and performed informed actions aiming to influence curriculum development and research culture. The interplay between personal and social resources we found influences teachers achieving of professional agency. Implications for future research include more in-depth analysis of this interplay of resources in achieving agency

Simplivariate Models: Ideas and First Examples

One of the new expanding areas in functional genomics is metabolomics: measuring the metabolome of an organism. Data being generated in metabolomics studies are very diverse in nature depending on the design underlying the experiment. Traditionally, variation in measurements is conceptually broken down in systematic variation and noise where the latter contains, e.g. technical variation. There is increasing evidence that this distinction does not hold (or is too simple) for metabolomics data. A more useful distinction is in terms of informative and non-informative variation where informative relates to the problem being studied. In most common methods for analyzing metabolomics (or any other high-dimensional x-omics) data this distinction is ignored thereby severely hampering the results of the analysis. This leads to poorly interpretable models and may even obscure the relevant biological information. We developed a framework from first data analysis principles by explicitly formulating the problem of analyzing metabolomics data in terms of informative and non-informative parts. This framework allows for flexible interactions with the biologists involved in formulating prior knowledge of underlying structures. The basic idea is that the informative parts of the complex metabolomics data are approximated by simple components with a biological meaning, e.g. in terms of metabolic pathways or their regulation. Hence, we termed the framework ‘simplivariate models’ which constitutes a new way of looking at metabolomics data. The framework is given in its full generality and exemplified with two methods, IDR analysis and plaid modeling, that fit into the framework. Using this strategy of ‘divide and conquer’, we show that meaningful simplivariate models can be obtained using a real-life microbial metabolomics data set. For instance, one of the simple components contained all the measured intermediates of the Krebs cycle of E. coli. Moreover, these simplivariate models were able to uncover regulatory mechanisms present in the phenylalanine biosynthesis route of E. coli

Polarised Asymmetric Inheritance of Accumulated Protein Damage in Higher Eukaryotes

Disease-associated misfolded proteins or proteins damaged due to cellular stress are generally disposed via the cellular protein quality-control system. However, under saturating conditions, misfolded proteins will aggregate. In higher eukaryotes, these aggregates can be transported to accumulate in aggresomes at the microtubule organizing center. The fate of cells that contain aggresomes is currently unknown. Here we report that cells that have formed aggresomes can undergo normal mitosis. As a result, the aggregated proteins are asymmetrically distributed to one of the daughter cells, leaving the other daughter free of accumulated protein damage. Using both epithelial crypts of the small intestine of patients with a protein folding disease and Drosophila melanogaster neural precursor cells as models, we found that the inheritance of protein aggregates during mitosis occurs with a fixed polarity indicative of a mechanism to preserve the long-lived progeny

Ins and Outs of Cerebellar Modules

The modular concept of cerebellar connections has been advocated in the lifetime work of Jan Voogd. In this concept, a cerebellar module is defined as the conglomerate of one or multiple and non-adjacent, parasagittally arranged zones of Purkinje cells, their specific projection to a well-defined region of the cerebellar nuclei, and the climbing fiber input to these zones by a well-defined region of the inferior olivary complex. The modular organization of these olivo-cortico-nuclear connections is further exemplified by matching reciprocal connections between inferior olive and cerebellar nuclei. Because the different regions of the cerebellar nuclei show highly specific output patterns, cerebellar modules have been suggested to constitute functional entities. This idea is strengthened by the observation that anatomically defined modules adhere to the distribution of chemical markers in the cerebellar cortex suggesting that modules not only differ in their input and output relations but also may differ in operational capabilities. Here, I will briefly review some recent data on the establishment of cerebellar modules in rats. Furthermore, some evidence will be shown suggesting that the other main afferent system (i.e., mossy fibers), at least to some extent, also adheres to the modular organization. Finally, using retrograde transneuronal tracing with rabies virus, some evidence will be provided that several cerebellar modules may be involved in the control of individual muscles