Cerebellar Modules and Their Role as Operational Cerebellar Processing Units

The compartmentalization of the cerebellum into modules is often used to discuss its function. What, exactly, can be considered a module, how do they operate, can they be subdivided and do they act individually or in concert are only some of the key questions discussed in this consensus paper. Experts studying cerebellar compartmentalization give their insights on the structure and function of cerebellar modules, with the aim of providing an up-to-date review of the extensive literature on this subject. Starting with an historical perspective indicating that the basis of the modular organization is formed by matching olivocorticonuclear connectivity, this is followed by consideration of anatomical and chemical modular boundaries, revealing a relation between anatomical, chemical, and physiological borders. In addition, the question is asked what the smallest operational unit of the cerebellum might be. Furthermore, it has become clear that chemical diversity of Purkinje cells also results in diversity of information processing between cerebellar modules. An additional important consideration is the relation between modular compartmentalization and the organization of the mossy fiber system, resulting in the concept of modular plasticity. Finally, examination of cerebellar output patterns suggesting cooperation between modules and recent work on modular aspects of emotional behavior are discussed. Despite the general consensus that the cerebellum has a modular organization, many questions remain. The authors hope that this joint review will inspire future cerebellar research so that we are better able to understand how this brain structure makes its vital contribution to behavior in its most general form

Pre and Post Synaptic NMDA Effects Targeting Purkinje Cells in the Mouse Cerebellar Cortex

N-methyl-D-aspartate (NMDA) receptors are associated with many forms of synaptic plasticity. Their expression level and subunit composition undergo developmental changes in several brain regions. In the mouse cerebellum, beside a developmental switch between NR2B and NR2A/C subunits in granule cells, functional postsynaptic NMDA receptors are seen in Purkinje cells of neonate and adult but not juvenile rat and mice. A presynaptic effect of NMDA on GABA release by cerebellar interneurons was identified recently. Nevertheless whereas NMDA receptor subunits are detected on parallel fiber terminals, a presynaptic effect of NMDA on spontaneous release of glutamate has not been demonstrated. Using mouse cerebellar cultures and patch-clamp recordings we show that NMDA facilitates glutamate release onto Purkinje cells in young cultures via a presynaptic mechanism, whereas NMDA activates extrasynaptic receptors in Purkinje cells recorded in old cultures. The presynaptic effect of NMDA on glutamate release is also observed in Purkinje cells recorded in acute slices prepared from juvenile but not from adult mice and requires a specific protocol of NMDA application

Can the intake of antiparasitic secondary metabolites explain the low prevalence of hemoparasites among wild Psittaciformes?

Background: Parasites can exert selection pressure on their hosts through effects on survival, on reproductive success, on sexually selected ornament, with important ecological and evolutionary consequences, such as changes in population viability. Consequently, hemoparasites have become the focus of recent avian studies. Infection varies significantly among taxa. Various factors might explain the differences in infection among taxa, including habitat, climate, host density, the presence of vectors, life history and immune defence. Feeding behaviour can also be relevant both through increased exposure to vectors and consumption of secondary metabolites with preventative or therapeutic effects that can reduce parasite load. However, the latter has been little investigated. Psittaciformes (parrots and cockatoos) are a good model to investigate these topics, as they are known to use biological control against ectoparasites and to feed on toxic food. We investigated the presence of avian malaria parasites (Plasmodium), intracellular haemosporidians (Haemoproteus, Leucocytozoon), unicellular flagellate protozoans (Trypanosoma) and microfilariae in 19 Psittaciformes species from a range of habitats in the Indo-Malayan, Australasian and Neotropical regions. We gathered additional data on hemoparasites in wild Psittaciformes from the literature. We considered factors that may control the presence of hemoparasites in the Psittaciformes, compiling information on diet, habitat, and climate. Furthermore, we investigated the role of diet in providing antiparasitic secondary metabolites that could be used as self-medication to reduce parasite load. Results: We found hemoparasites in only two of 19 species sampled. Among them, all species that consume at least one food item known for its secondary metabolites with antimalarial, trypanocidal or general antiparasitic properties, were free from hemoparasites. In contrast, the infected parrots do not consume food items with antimalarial or even general antiparasitic properties. We found that the two infected species in this study consumed omnivorous diets. When we combined our data with data from studies previously investigating blood parasites in wild parrots, the positive relationship between omnivorous diets and hemoparasite infestation was confirmed. Individuals from open habitats were less infected than those from forests. Conclusions: The consumption of food items known for their secondary metabolites with antimalarial, trypanocidal or general antiparasitic properties, as well as the higher proportion of infected species among omnivorous parrots, could explain the low prevalence of hemoparasites reported in many vertebrates

Intégration spatiale et temporelle des entrées granulaires dans le cortex cérébelleux

Using whole cell patch clamp recording in rat cerebellum acute slices, I found that high frequency information processed in mossy fibre (MF)-granule cell (GC) pathway is conseved at the GC-Purkinje cell (PC) synapse. Bursts of action potential could evoke strong, excitatory postsynaptic currents at the PC soma that can follow high frequency rates, with high initial release probability, paired-pulse facilitation up to 700 Hz, and sustained facilitation during tensof pulses. This fast and sustained release is possible during bursts through the recruitment of reluctant vesicles that boost vesicular release. In a second study, by using precise RuBi-Glutamate uncaging onto granule cells, and by recording either PC, molecular layer interneurons or Golgi cells, 1 found that in the anterior vermis of the mouse cerebellum, GC-PC connection follows a precise spatial organisation. Specifie sets of PC, that can be identified using histochemical markers, receive inputs from small GC hotspots.En utilisant des enregistrements en patch-clamp sur des tranches aigues de cervelet de rat, j'ai observé que les informations à haute fréquence traitées dans la voie fibre moussues (FM)-cellules granulaires (CG) sont conservées à la synapse CG-cellule de Purkinje (CP). Des trains de potentiels d'action évoquent des courants postsynaptiques excitateurs importants, même à haute fréquence, avec une haute probabilité de libération initiale, une forte facilitation jusqu'à 700Hz, et ceci de façon soutenue. Ce mécanisme est possible grâce au recrutement de vésicules initialement réfractaires. Une seconde étude utilisant du decageage de Rubi-Glutamate sur les CG a permis de révéler une organisation spatialeprécise des connexions CG-PC, CG-Interneurones de la couche moléculaire (ICM) et CG-Cellules de Golgi (CGo). Des groupes spécifiques de CP/CGo ou ICM, identifiables via des marqueurs histochimiques sont contacté par des populations spécifiques de CG

Stereotyped spatial patterns of functional synaptic connectivity in the cerebellar cortex

International audienc

Response to Prone Position in COVID-19 and Non-COVID-19 Patients with Severe ARDS Supported by vvECMO

Background: For moderate to severe acute respiratory distress syndrome (ARDS), lung-protective ventilation combined with prolonged and repeated prone position (PP) is recommended. For the most severe patients for whom this strategy failed, venovenous extracorporeal membrane oxygenation (vv-ECMO) allows a reduction in ventilation-induced lung injury and improves survival. Some aggregated data have suggested a benefit regarding survival in pursuing PP during vv-ECMO. The combination of PP and vv-ECMO has been also documented in COVID-19 studies, although there is scarce evidence concerning respiratory mechanics and gas exchange response. The main objective was to compare the physiological response of the first PP during vv-ECMO in two cohorts of patients (COVID-19-related ARDS and non-COVID-19 ARDS) regarding respiratory system compliance (CRS) and oxygenation changes. Methods: This was a single-center, retrospective, and ambispective cohort study in the ECMO center of Marseille, France. ECMO was indicated according to the EOLIA trial criteria. Results: A total of 85 patients were included, 60 in the non-COVID-19 ARDS group and 25 in the COVID-19-related ARDS group. Lung injuries of the COVID-19 cohort exhibited significantly higher severity with a lower CRS at baseline. Concerning the main objective, the first PP during vv-ECMO was not associated with a change in CRS or other variation in respiratory mechanic variables in both cohorts. By contrast, oxygenation was improved only in the non-COVID-19 ARDS group after a return to the supine position. Mean arterial pressure was higher during PP as compared with a return to the supine position in the COVID-19 group. Conclusion: We found distinct physiological responses to the first PP in vv-ECMO-supported ARDS patients according to the COVID-19 etiology. This could be due to higher severity at baseline or specificity of the disease. Further investigations are warranted

Diagnostic developments at CERN’s SRF testing facility

As part of CERN’s re-establishment of an SRF cold testing facility for bulk niobium cavities, diagnostic instrumentation and testing procedures on our vertical cryostat have been upgraded, with particular attention given to quench location, ambient magnetic field control, thermometry and thermal cycling techniques. In addition, preparation and measurement procedures have been addressed, allowing for improved measurement of cavity properties and detailed study of transient effects during the course of cavity testing

Repetitive applications of NMDA promote the facilitatory effect on mEPSC frequency.

<p>A. Current traces showing mEPSCs before (left) and after (right) a second application of NMDA. B (same cell as in A). Histogram representing the number of mEPSCs as a function of recording time (bin 10 s). During the short horizontal bars NMDA is applied at 10⁻⁵ M (bars 1 and 2) and at 5×10⁻⁶ M. (bar 3). C. Cumulative plots of inter-event intervals in control conditions (black curve) in the presence of NMDA after the first application (1, red curves) and second application (2, blue curve).</p

Summary of NMDA effects on mEPSCs recorded in Purkinje cells recorded from slice cultures.

<p>Graph on the left represents % Purkinje cells in which an NMDA-mediated increase in mEPSC frequency is observed as a function of Purkinje cell age. Graphs in middle and on the right represent respectively the mEPSC mean frequency and mean amplitude before and after the first application NMDA recorded in Purkinje cells from 12–22 day old slice cultures. A representation with box plots indicating the mean values (thick line) and median values (thin line) has been adopted because of the non-normal distribution of mean frequency and mean amplitude values. The bottom and the top of the box represent the 25^th and 75 th percentile respectively. The ends of the whiskers represent the 5^th/95^th percentile.</p