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

Cerebellar Zones: A Personal History

Cerebellar zones were there, of course, before anyone noticed them. Their history is that of young people, unhindered by preconceived ideas, who followed up their observations with available or new techniques. In the 1960s of the last century, the circumstances were fortunate because three groups, in Leiden, Lund, and Bristol, using different approaches, stumbled on the same zonal pattern in the cerebellum of the cat. In Leiden, the Häggqvist myelin stain divulged the compartments in the cerebellar white matter that channel the afferent and efferent connections of the zones. In Lund, the spino-olivocerebellar pathways activated from individual spinal funiculi revealed the zonal pattern. In Bristol, charting the axon reflex of olivocerebellar climbing fibers on the surface of the cerebellum resulted in a very similar zonal map. The history of the zones is one of accidents and purposeful pursuit. The technicians, librarians, animal caretakers, students, secretaries, and medical illustrators who made it possible remain unnamed, but their contributions certainly should be acknowledged

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

Lens epithelial cell layer formation related to hydrogel foldable intraocular lenses

Purpose: To determine the incidence of postoperative lens epithelial cel (LEC) layer formation anterior to the Hydroview hydrogel foldable intraocular lens (IOL), the effect on vision, and the appearance under scanning electron microscopy (SEM). Setting: Eye Unit of district general hospital, Delfzijl, and the Laboratory for Cell Biology and electron Microscopy, Faculty of Medical Sciences, University of Groningen, The Netherlands. Methods: In this prospective study, 207 eyes that received a Hydroview hydrogel foldable IOL during 1996 were followed for almost 2 years (range 8 to 98 weeks). Eleven eyes had follow-up of fewer than 8 weeks and were excluded. Some eyes had a transparent to milky-white membrane anterior to the IOL in the plane of capsulorhexis. In the absence of other contributing factors, if best corrected visual acuity was worse than expected, it was assumed to be caused by the membrane. Depending on the membrane's thickness, determined at the slitlamp, patients were offered a neodymium:YAG (Nd:YAG) laser or surgical membranectomy. If surgically excised, the layer was studied by SEM. Results: Of the 196 eyes, 62 eyes (33.16%) developed a thin epithelial cell layer. The membrane appeared a mean of 38.5 weeks postoperatively (range 9.9 to 85.6 weeks). Eleven eyes (5.61%) had visual symptoms varying from low vision to hazy vision or light scatter. Visual symptoms were present even in cases in which the visual axis was not invaded by the membrane. Once this layer was removed surgically or by the Nd:YAG laser, vision improved and symptoms were relieved. Four eyes (2.04%) required a surgical membranectomy. Examination of these removed membranes by SEM showed their multilayer nature and that the LECs had differentiated into fibroblast-like cells with collagenous fibrils and extracellular matrix. Conclusions: The incidence of LEC membrane formation was higher than expected and increased with time in eyes with a Hydroview IOL. The membrane caused visual symptoms by occluding the visual axis, causing striation on the membrane and the IOL to decenter, tilt, or fold. These symptoms improved after the membrane was removed. J Cataract Refract Surg 1999: 25:1637-1640 (C) 1999 ASCRS and ESCRS

Lens epithelial cell layer formation related to hydrogel foldable intraocular lenses

Purpose: To determine the incidence of postoperative lens epithelial cel (LEC) layer formation anterior to the Hydroview hydrogel foldable intraocular lens (IOL), the effect on vision, and the appearance under scanning electron microscopy (SEM). Setting: Eye Unit of district general hospital, Delfzijl, and the Laboratory for Cell Biology and electron Microscopy, Faculty of Medical Sciences, University of Groningen, The Netherlands. Methods: In this prospective study, 207 eyes that received a Hydroview hydrogel foldable IOL during 1996 were followed for almost 2 years (range 8 to 98 weeks). Eleven eyes had follow-up of fewer than 8 weeks and were excluded. Some eyes had a transparent to milky-white membrane anterior to the IOL in the plane of capsulorhexis. In the absence of other contributing factors, if best corrected visual acuity was worse than expected, it was assumed to be caused by the membrane. Depending on the membrane's thickness, determined at the slitlamp, patients were offered a neodymium:YAG (Nd:YAG) laser or surgical membranectomy. If surgically excised, the layer was studied by SEM. Results: Of the 196 eyes, 62 eyes (33.16%) developed a thin epithelial cell layer. The membrane appeared a mean of 38.5 weeks postoperatively (range 9.9 to 85.6 weeks). Eleven eyes (5.61%) had visual symptoms varying from low vision to hazy vision or light scatter. Visual symptoms were present even in cases in which the visual axis was not invaded by the membrane. Once this layer was removed surgically or by the Nd:YAG laser, vision improved and symptoms were relieved. Four eyes (2.04%) required a surgical membranectomy. Examination of these removed membranes by SEM showed their multilayer nature and that the LECs had differentiated into fibroblast-like cells with collagenous fibrils and extracellular matrix. Conclusions: The incidence of LEC membrane formation was higher than expected and increased with time in eyes with a Hydroview IOL. The membrane caused visual symptoms by occluding the visual axis, causing striation on the membrane and the IOL to decenter, tilt, or fold. These symptoms improved after the membrane was removed. J Cataract Refract Surg 1999: 25:1637-1640 (C) 1999 ASCRS and ESCRS

The localisation of urocortin in the adult rat cerebellum: A light and electron microscopic study

Light and electron microscopic immunocytochemistry was used to identify the cellular and subcellular localisation of urocortin in the adult rat cerebellum. Urocortin immunoreactivity (UCN-ir) was visualised throughout the cerebellum, yet predominated in the posterior vermal lobules, especially lobules IX and X, the flocculus, paraflocculus and deep cerebellar nuclei. Cortical immunoreactivity was most evident in the Purkinje cell layer and molecular layer. Reaction product, though sparse, was found in the somata of Purkinje cells, primarily in the region of the Golgi apparatus. Purkinje cell dendritic UCN-ir was compartmentalised, with it being prevalent in proximal regions especially where climbing fibres synapsed, yet absent in distal regions where parallel fibres synapsed. In the Purkinje cell layer, the labelling was also contained in axonal terminals, synapsing directly on Purkinje cell somata. These were identified as axon terminals of basket cells based on their morphology. Terminals of stellate cells in the upper molecular layer also expressed the peptide. Whilst somata of inferior olivary neurones showed intense immunoreactivity, axonal labelling was indistinct, with only the terminals of climbing fibres containing reaction product. UCN-ir in the mossy fibre-parallel fibre system was restricted to mossy fibre rosettes of mainly posterior lobules and the varicose terminals of parallel fibres. Furthermore, labelling also was prevalent in glial perikarya and their sheaths. The current study shows, firstly, that urocortin enjoys a close ligand-receptor symmetry in the cerebellum, probably to a greater degree than corticotropin-releasing factor since corticotropin-releasing factor itself is found exclusively in the two major cerebellar afferent systems. Its congregation in excitatory and inhibitory axonal terminals suggests a significant degree of participation in the synaptic milieu, perhaps in the capacity as a neurotransmitter or effecting the release of colocalised neurotransmitters. Finally, its unique distribution in the Purkinje cell dendrite might serve as an anatomical marker of discrete populations of dendritic spines. (C) 2002 IBRO. Published by Elsevier Science Ltd. All rights reserved