Cerebellar Zones: History, Development, and Function

Oberdick, John; Sillitoe, Roy V.

doi:10.1007/s12311-011-0306-x

Cited by 19 publications

(11 citation statements)

References 50 publications

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“…These injections retrogradely labeled somata in the anterior interposed nucleus, consistent with reports of topographical organization of the nucleocortical pathway in other species (n=5/6; Fig. 2B; Gould and Graybiel, 1976; Tolbert et al, 1976; Dietrichs and Walberg, 1979, 1980) and the general topographic arrangement of mossy fiber and intracerebellar organization (Oberdick and Sillitoe, 2011). Injections that retrogradely labeled somata in the CbN also labeled axons and terminals but not somata in the contralateral ventrolateral thalamus and red nucleus (n=9; Fig.…”

Section: Resultssupporting

confidence: 89%

Cerebellar premotor output neurons collateralize to innervate the cerebellar cortex

Houck

Person

2015

J of Comparative Neurology

101

118

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Motor commands computed by the cerebellum are hypothesized to use corollary discharge, or copies of outgoing commands, to accelerate motor corrections. Identifying sources of corollary discharge, therefore, is critical for testing this hypothesis. Here, we verified that the pathway from the cerebellar nuclei to the cerebellar cortex in mice includes collaterals of cerebellar premotor output neurons, mapped this collateral pathway, and identified its postsynaptic targets. Following bidirectional tracer injections into a distal target of the cerebellar nuclei, the ventrolateral thalamus, we observed retrogradely labeled somata in the cerebellar nuclei and mossy fiber terminals in the cerebellar granule layer, consistent with collateral branching. Corroborating these observations, bidirectional tracer injections into the cerebellar cortex retrogradely labeled somata in the cerebellar nuclei and boutons in the ventrolateral thalamus. To test whether nuclear output neurons projecting to the red nucleus also collateralize to the cerebellar cortex, we used a Cre-dependent viral approach, avoiding potential confounds of direct red nucleus-to-cerebellum projections. Injections of a Cre-dependent GFP-expressing virus into Ntsr1-Cre mice, which express Cre selectively in the cerebellar nuclei, retrogradely labeled somata in the interposed nucleus and putative collateral branches terminating as mossy fibers in the cerebellar cortex. Postsynaptic targets of all labeled mossy fiber terminals were identified using immunohistochemical Golgi cell markers and electron microscopic profiles of granule cells, indicating that the collaterals of nuclear output neurons contact both Golgi and granule cells. These results clarify the organization of a subset of nucleocortical projections which constitute an experimentally accessible corollary discharge pathway within the cerebellum.

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Section: Resultssupporting

confidence: 89%

Cerebellar premotor output neurons collateralize to innervate the cerebellar cortex

Houck

Person

2015

J of Comparative Neurology

101

118

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“…A module is a conglomerate of several, non-adjacent parasagittal bands of Purkinje cells projecting to specific areas of deep cerebellar nuclei and gating segregated projections from the inferior olive (Cerminara, 2010; Oberdick and Sillitoe, 2011; Ruigrok, 2010). Likewise, the mossy fibers projecting to a certain group of Purkinje cells through the granular layer also project to the same deep cerebellar nucleus neuron receiving input from those Purkinje cells (Ito, 1984; Pijpers et al, 2006; Voogd, 2010).…”

Section: The Extended Cerebro-cerebellar Loopsmentioning

confidence: 99%

Seeking a unified framework for cerebellar function and dysfunction: from circuit operations to cognition

D’Angelo

Casali²

2013

Front. Neural Circuits

261

282

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Following the fundamental recognition of its involvement in sensory-motor coordination and learning, the cerebellum is now also believed to take part in the processing of cognition and emotion. This hypothesis is recurrent in numerous papers reporting anatomical and functional observations, and it requires an explanation. We argue that a similar circuit structure in all cerebellar areas may carry out various operations using a common computational scheme. On the basis of a broad review of anatomical data, it is conceivable that the different roles of the cerebellum lie in the specific connectivity of the cerebellar modules, with motor, cognitive, and emotional functions (at least partially) segregated into different cerebro-cerebellar loops. We here develop a conceptual and operational framework based on multiple interconnected levels (a meta-levels hypothesis): from cellular/molecular to network mechanisms leading to generation of computational primitives, thence to high-level cognitive/emotional processing, and finally to the sphere of mental function and dysfunction. The main concept explored is that of intimate interplay between timing and learning (reminiscent of the “timing and learning machine” capabilities long attributed to the cerebellum), which reverberates from cellular to circuit mechanisms. Subsequently, integration within large-scale brain loops could generate the disparate cognitive/emotional and mental functions in which the cerebellum has been implicated. We propose, therefore, that the cerebellum operates as a general-purpose co-processor, whose effects depend on the specific brain centers to which individual modules are connected. Abnormal functioning in these loops could eventually contribute to the pathogenesis of major brain pathologies including not just ataxia but also dyslexia, autism, schizophrenia, and depression.

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“…In these clusters, the excitatory-inhibitory (E/I) balance is higher in the core, thus leading to the formation of a center-surround structure (Mapelli and D'Angelo, 2007). It is also important to consider how Golgi cell connectivity is related to the modular organization of the cerebellar cortex [(Voogd et al, 2003; Apps and Hawkes, 2009; Oberdick and Sillitoe, 2011); for a recent review see (D'Angelo and Casali, 2012)] 2 . At this level, the granular layer performs complex operations of spatiotemporal recoding of the mossy fiber input, which can be recognized by analyzing intermodular connectivity and signal transmission along the vertical and transverse axis of the cerebellar cortex (Bower and Woolston, 1983; Mapelli et al, 2010a,b).…”

Section: Functional Connectivity: Expanding the Viewmentioning

confidence: 99%

“…These have a complex relationships with stripes, zones and multizonal microcomplexes, which are also though to represent effective functional modules (Apps and Hawkes, 2009). A module is a conglomerate of several, non-adjacent parasagittal bands of Purkinje cells projecting to specific areas of deep cerebellar nuclei and gating segregated projections from the inferior olive (Oberdick and Sillitoe, 2011). Likewise, the mossy fibers projecting to a certain group of Purkinje cells through the granular layer also project to the deep cerebellar nucleus neuron receiving input from those Purkinje cells (Voogd et al, 2003).…”

mentioning

confidence: 99%

The cerebellar Golgi cell and spatiotemporal organization of granular layer activity

D’Angelo

Solinas²,

Mapelli

et al. 2013

Front. Neural Circuits

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The cerebellar granular layer has been suggested to perform a complex spatiotemporal reconfiguration of incoming mossy fiber signals. Central to this role is the inhibitory action exerted by Golgi cells over granule cells: Golgi cells inhibit granule cells through both feedforward and feedback inhibitory loops and generate a broad lateral inhibition that extends beyond the afferent synaptic field. This characteristic connectivity has recently been investigated in great detail and been correlated with specific functional properties of these neurons. These include theta-frequency pacemaking, network entrainment into coherent oscillations and phase resetting. Important advances have also been made in terms of determining the membrane and synaptic properties of the neuron, and clarifying the mechanisms of activation by input bursts. Moreover, voltage sensitive dye imaging and multi-electrode array (MEA) recordings, combined with mathematical simulations based on realistic computational models, have improved our understanding of the impact of Golgi cell activity on granular layer circuit computations. These investigations have highlighted the critical role of Golgi cells in: generating dense clusters of granule cell activity organized in center-surround structures, implementing combinatorial operations on multiple mossy fiber inputs, regulating transmission gain, and cut-off frequency, controlling spike timing and burst transmission, and determining the sign, intensity and duration of long-term synaptic plasticity at the mossy fiber-granule cell relay. This review considers recent advances in the field, highlighting the functional implications of Golgi cells for granular layer network computation and indicating new challenges for cerebellar research.

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Cerebellar Zones: History, Development, and Function

Cited by 19 publications

References 50 publications

Cerebellar premotor output neurons collateralize to innervate the cerebellar cortex

Cerebellar premotor output neurons collateralize to innervate the cerebellar cortex

Seeking a unified framework for cerebellar function and dysfunction: from circuit operations to cognition

The cerebellar Golgi cell and spatiotemporal organization of granular layer activity

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