Biology subjects

Hoebeek, F. E.

Publications and source records attributed to Hoebeek, F. E..

3 recordsLinked to original sources

bioRxiv2020

Uneven distribution of Purkinje cell injury in the cerebellar vermis of term neonates with hypoxic-ischemic encephalopathy

IntroductionIn term neonates with hypoxic-ischemic encephalopathy (HIE), cerebellar injury is becoming more and more acknowledged. Animal studies demonstrated that Purkinje cells (PCs) are especially vulnerable for hypoxic-ischemic injury. In neonates, however, the extent and pattern of PC injury has not been investigated. The aim of this study was to determine the distribution of PC injury in the cerebellar vermis of term born neonates with HIE. MethodsTerm born neonates with HIE that underwent post-mortem autopsy of the cerebellar vermis were included. Haematoxylin & Eosin (H&E) stained sections of the vermis were used to determine total PC count and morphology (normal, abnormal or non-classified) at the bases and crown of the folia and of the lobules in both the anterior and posterior lobes. Differences in PC count and PC morphology between the anterior and posterior lobe and between the bases and crown were calculated using the paired samples T-test or Wilcoxon-signed rank test. ResultsThe total number of PCs were significantly higher at the crown compared to the bases (p<0.001) irrespective of the precise location. Besides, PCs at the bases more often had an abnormal morphology. No significant difference between the total number of PCs in the anterior and posterior lobe was observed. ConclusionThe abnormal PC count and morphology in term neonates with HIE resembles supratentorial ulegyria.

neuroscience↗

bioRxiv2020

Cerebello-Thalamic Spike Transfer via Temporal Coding and Cortical Adaptation

Orchestrating the ensemble of muscle contractions necessary for coordinated movements requires the interaction of cerebellar, thalamic and cerebral structures, but the mechanisms underlying the integration of information remain largely unknown. Here we investigated how excitatory inputs from cerebellar nuclei (CN) and primary motor cortex layer VI (M1 L6) neurons may regulate together the activity of neurons in the mouse ventrolateral (VL) thalamus. Using dual-optogenetic stimulation and whole-cell recordings in vitro we were able to specifically activate the CN and M1 pathways and study their differential impact. We found that VL spiking probability is effectively determined by a pause in CN stimuli, whereas VL membrane potential can be modulated subthreshold by M1 L6 input. Upon mild depolarization of the VL membrane potential, repetitive CN stimulation evokes at best single action potential firing, whereas more negative membrane potentials increase VL spiking probability. Moreover, whereas high-frequency cerebellar activity attenuates thalamic spiking, pauses in cerebellar activity re-activate thalamic spiking. In contrast, facilitating inputs from cerebral cortex modulate thalamo-cortical spike transfer via fluctuations in the membrane potential. The fine-tuning by cerebellar and cerebral activity allows the motor thalamus to operate as a low-pass filter for cerebellar activity, generating sparse but precisely timed outputs for the cerebral cortex.

neuroscience↗

bioRxiv2019

Anatomical development of the cerebellothalamic tract in embryonic mice

Cerebellar projections to the thalamus are a pivotal connection in cerebello-cerebral interactions. Apart from its role in coordinating sensorimotor integration in the adult brain, the cerebello-thalamic projection has also been implemented in developmental disorders, such as autism spectrum disorders. Although the development of the cerebellum, thalamus and cerebral cortex have been studied in many species, a detailed description of the ontogeny of the mammalian cerebello-thalamic tract (CbT) is currently missing. Here we investigated the development of the CbT at embryonic stages using transgenic Ntsr1-Cre/Ai14 mice and in utero electroporation (IUE) of wild type mice. Wide-field, confocal and 3D light-sheet imaging of immunohistochemical stainings showed that CbT fibers arrive in the prethalamus between E14.5 and E15.5, but only invade the thalamus after E16.5. We quantified the spread of CbT fibers throughout the various thalamic nuclei and found that at E17.5 and E18.5 the ventrolateral, ventromedial and parafascicular nuclei, but also the mediodorsal and posterior complex become increasingly innervated. Several CbT fiber varicosities colocalize with vGluT2, indicating that already from E18.5 the CbT synapse in various thalamic nuclei. Our results contribute to the construction of a frame of reference on the anatomical development of the CbT, which will help to guide future experiments investigating neurodevelopmental disorders.\n\nSignificance statementUsing various microscopic approaches, we investigated the anatomical development of the fiber tract between the cerebellum and thalamus, one of the major mammalian brain connections. Our results show that in mice cerebellar axons wait outside of the thalamus from embryonic day (E)15.5 until E17.5 before invading the thalamic complex. Cerebellar axons establish vGluT2-positive synapses at E18.5 throughout various thalamic nuclei, each of which subsequently develops its connections with dedicated cerebral cortical regions. Our data thereby advocate the cerebellar influence on the maturation of the thalamus and connected cerebral cortex. This knowledge can help to guide future experiments into neurodevelopmental disorders affecting cerebello-thalamo-cortical networks.

neuroscience↗