RESUMEN
The cerebellar intrinsic connectivity is of remarkable regularity with a similar build repeated many times over. However, several modifications of this basic circuitry occur that can provide important clues to evolutionary adaptations. We have observed differences in the wiring of the cerebellar output structures (the deep cerebellar nuclei, DCN) with higher dendritic length density in the phylogenetically newer DCN. In rats, we showed that an increase in wiring is associated with an increase in the presynaptic vesicular glutamate transporter 1 (vGluT1). In this study, we have extended our analysis to the rhesus monkey and can show similarities and differences between the two species. The similarities confirm a higher density in vGluT1+ boutons in the lateral (LN/dentate) and posterior interpositus nucleus compared to the phylogenetically older DCN. In general, we also observe a lower density of vGluT1 and 2+ boutons in the monkey, which however, yields a similar number of excitatory boutons per neuron in both species. The only exception is the vGlut1+ boutons in the macaque LN/dentate, which showed a significantly lower number of vGluT1+ boutons per neuron. We also detected a higher percentage of co-labelled vGluT1 and 2 boutons in the macaque than we found in the rat. In summary, these results confirm that the hyposcalled dendrites of the monkey LN/dentate also show a lower number of vGluT1+ boutons per neuron. These results provide further support of our model relating the dendritic morphology of the LN/dentate neurons to the morphology of the specially enlarged LN/dentate nucleus in primates.
Asunto(s)
Núcleos Cerebelosos/patología , Cerebelo/patología , Terminales Presinápticos/patología , Sinapsis/patología , Animales , Axones/metabolismo , Axones/patología , Núcleos Cerebelosos/metabolismo , Cerebelo/metabolismo , Dendritas/metabolismo , Dendritas/patología , Macaca mulatta , Masculino , Neuronas/metabolismo , Neuronas/patología , Terminales Presinápticos/metabolismo , Sinapsis/metabolismoRESUMEN
The excitatory synapses of the rat deep cerebellar nuclei (DCN) were quantitatively analyzed by vesicular glutamate transporter 1 and 2 (vGluT1 and vGluT2) immunolabeling. We calculated the number and sizes of the labeled boutons and compared them between lateral/dentate nucleus (LN/DN), posterior interposed nucleus (PIN), anterior interposed nucleus (AIN), and medial nucleus (MN). The density of vGluT1+ boutons differs significantly within these nuclei. In contrast, the vGluT2+ bouton density is more similar between different nuclei. The phylogenetically newer DCN (LN/DN and PIN) have a 39% higher density of vGluT1+ boutons than the phylogenetically older DCN (AIN and MN). The volume of vGluT1+ boutons does not differ between the DCN, however the average volume of vGluT2+ boutons is larger in MN. In summary, our current results confirm and extend our previous findings showing that the increase in dendritic and axonal wiring in phylogenetically newer DCN is associated with an increase in vGluT1+ bouton density.
Asunto(s)
Núcleos Cerebelosos/metabolismo , Proteína 1 de Transporte Vesicular de Glutamato/metabolismo , Proteína 2 de Transporte Vesicular de Glutamato/metabolismo , Animales , Núcleos Cerebelosos/citología , Proteínas del Tejido Nervioso/metabolismo , Terminales Presinápticos/metabolismo , Ratas , Canales de Potasio Shaw/metabolismoRESUMEN
Regular scaling of brain networks during evolution has been proposed to be the major process leading to enlarged brains. Alternative views, however, suggest that deviations from regular scaling were crucial to the evolution of the primate brain and the emergence of different cerebrotypes. Here, we examined the scaling within the major link between the cerebellum and the cerebral cortex by studying the deep cerebellar nuclei (DCN). We compared the major axonal and dendritic wiring in the DCN of rodents and monkeys in search of regular scaling. We were able to confirm regular scaling within the density of neurons, the general dendritic length per neuron and the Purkinje cell axon length. However, we also observed specific modification of the scaling rules within the primates' largest and phylogenetically newest DCN, the dentate nucleus (LN/dentate). Our analysis shows a deviation from regular scaling in the predicted dendritic length per neuron in the LN/dentate. This reduction in the dendritic length is also associated with a smaller dendritic region-of-influence of these neurons. We also detected specific changes in the dendritic diameter distribution, supporting the theory that there is a shift in the neuronal population of the LN/dentate towards neurons that exhibit spatially restricted, clustered branching trees. The smaller dendritic fields would enable a larger number of network modules to be accommodated in the primate LN/dentate and would provide an explanation for the unique folded structure of the primate LN/dentate. Our results show that, in some brain regions, connectivity maximization (i.e., an increase of dendritic fields) is not the sole optimum and that increases in the number of network modules may be important for the emergence of a divergent primate cerebrotype.
Asunto(s)
Núcleos Cerebelosos/citología , Corteza Cerebral/fisiología , Vías Nerviosas/citología , Neuronas/fisiología , Especificidad de la Especie , Acetiltransferasas/metabolismo , Análisis de Varianza , Animales , Axones/metabolismo , Mapeo Encefálico , Núcleos Cerebelosos/fisiología , Dendritas/metabolismo , Macaca mulatta , Masculino , Proteínas del Tejido Nervioso/metabolismo , Vías Nerviosas/fisiología , Neuroglía/citología , Neuroglía/metabolismo , Neuronas/citología , Impresión Tridimensional , RatasRESUMEN
A common view of the architecture of different brain regions is that, despite their heterogeneity, they have optimized their wiring schemes to make maximal use of space. Based on experimental findings, computational models have delineated how about two-thirds of the neuropil is filled out with dendrites and axons optimizing cable costs and conduction time while keeping the connectivity at the highest level. However, whether this assumption can be generalized to all brain regions has not yet been tested. Here we quantified and charted the components of the neuropil in the four deep cerebellar nuclei (DCN) of the rat's brain. We segmented and traced the neuropil stained with one of two antibodies, one antibody against dendritic microtubule-associated proteins (MAP2a,b) and the second against the Purkinje cell axons (PCP2). We compared fiber length density, average fiber diameter, and volume fraction within different components of the DCN in a random, systematic fashion. We observed differences in dendritic and axonal fiber length density, average fiber diameters, and volume fraction within the four different nuclei that make up the DCN. We observe a relative increase in the length density of dendrites and Purkinje cell axons in two of the DCN, namely, the posterior interposed nucleus and the lateral nucleus. Furthermore, the DCN have a surprisingly low volume fraction of their dendritic length density, which we propose is related to their special circuitry. In summary, our results show previously unappreciated functional adaptations among these nuclei.
Asunto(s)
Núcleos Cerebelosos/citología , Neuronas/citología , Análisis de Varianza , Animales , Axones/metabolismo , Recuento de Células , Núcleos Cerebelosos/metabolismo , Dendritas/metabolismo , Imagenología Tridimensional , Inmunohistoquímica , Macaca mulatta , Masculino , Microscopía Confocal , Proteínas Asociadas a Microtúbulos/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Vías Nerviosas/citología , Vías Nerviosas/metabolismo , Neuroglía/citología , Neuroglía/metabolismo , Neuronas/metabolismo , Neurópilo/metabolismo , Células de Purkinje/citología , Células de Purkinje/metabolismo , Ratas Sprague-Dawley , Especificidad de la EspecieRESUMEN
Increasing evidence has implicated the cerebellum in providing forward models of motor plants predicting the sensory consequences of actions. Assuming that cerebellar input to the cerebral cortex contributes to the cerebro-cortical processing by adding forward model signals, we would expect to find projections emphasising motor and sensory cortical areas. However, this expectation is only partially met by studies of cerebello-cerebral connections. Here we show that by electrically stimulating the cerebellar output and imaging responses with functional magnetic resonance imaging, evoked blood oxygen level-dependant activity is observed not only in the classical cerebellar projection target, the primary motor cortex, but also in a number of additional areas in insular, parietal and occipital cortex, including sensory cortical representations. Further probing of the responses reveals a projection system that has been optimized to mediate fast and temporarily precise information. In conclusion, both the topography of the stimulation effects and its emphasis on temporal precision are in full accordance with the concept of cerebellar forward model information modulating cerebro-cortical processing.
Asunto(s)
Cerebelo/fisiología , Vías Nerviosas/fisiología , Animales , Cerebelo/metabolismo , Estimulación Encefálica Profunda , Macaca mulatta , Imagen por Resonancia MagnéticaRESUMEN
Flattened representations are a useful approach to represent the convoluted complex surface of the neocortex of primates and other large-brained mammals. In this study, we compared the flattened representation of neocortical areas obtained from the recently published MRI and histology atlas of the rhesus monkey brain (Saleem KS, Logothetis NK. A combined MRI and histology atlas of the rhesus monkey brain in stereotaxic coordinates. London: Academic; 2007) with other previously published maps. Our results confirm that flat map representations are advantageous due to their ease of use and that current flat maps are well comparable to each other. Some differences arise due to different distinguishing criteria and here too flat maps can help to reveal them.