Maturation of Cerebellar Purkinje Cell Population Activity during Postnatal Refinement of Climbing Fiber Network

Good, Jean Marc; Mahoney, Michael J.; Miyazaki, Toru; Tanaka, Kenji F.; Sakimura, Kenji; Watanabe, Masahiko; Kitamura, Kazuhiro; Kano, Masanobu

doi:10.1016/j.celrep.2017.10.101

Cited by 23 publications

(19 citation statements)

References 32 publications

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“…In regard to the molecules that mediate activities of PCs, previous studies have shown that the P/Q-type voltage-dependent Ca 2+ channel (VDCC), the major VDCC in PCs, is essential for all four phases of CF synapse remodeling during postnatal cerebellar development 17, 22, 23 ( Figure 2). In addition, a study using in vivo whole-cell recording from single PCs 24 and a recent report of two-photon calcium imaging of PC population activities 25 strongly support that P/Q-VDCC is crucial for strengthening of single “winner” CF inputs ( Figure 2). On the other hand, the late phase of CF elimination has been shown to require the metabotropic glutamate receptor subtype 1 (mGluR1)–to–protein kinase Cγ (PKCγ) cascade in PCs 26– 31 , involves activation of the immediate early gene Arc 22, 32 , and is regulated by GABAergic inhibition of the PC soma by basket cells 33 ( Figure 2).…”

Section: Multiple Phases Of Developmental Cf-to-pc Synapse Remodelingmentioning

confidence: 62%

Developmental synapse remodeling in the cerebellum and visual thalamus

Kano

Watanabe

2019

F1000Res

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Functional neural circuits of mature animals are shaped during postnatal development by eliminating early-formed redundant synapses and strengthening of necessary connections. In the nervous system of newborn animals, redundant synapses are only transient features of the circuit. During subsequent postnatal development, some synapses are strengthened whereas other redundant connections are weakened and eventually eliminated. In this review, we introduce recent studies on the mechanisms of developmental remodeling of climbing fiber–to–Purkinje cell synapses in the cerebellum and synapses from the retina to neurons in the dorsal lateral geniculate nucleus of the visual thalamus (retinogeniculate synapses). These are the two representative models of developmental synapse remodeling in the brain and they share basic principles, including dependency on neural activity. However, recent studies have disclosed that, in several respects, the two models use different molecules and strategies to establish mature synaptic connectivity. We describe similarities and differences between the two models and discuss remaining issues to be tackled in the future in order to understand the general schemes of developmental synapse remodeling.

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Section: Multiple Phases Of Developmental Cf-to-pc Synapse Remodelingmentioning

confidence: 62%

Developmental synapse remodeling in the cerebellum and visual thalamus

Kano

Watanabe

2019

F1000Res

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“…We note, however, that additional mechanisms could work in parallel to effectively control the dimensionality, such as pruning of irrelevant inputs [80]. In the olivo-cerebellar system, in particular, climbing fiber-Purkinje-cell synapses are gradually eliminated based on IO activity during development [81,82]. We further note that our proposal of dimension reduction of an oscillatory system via coupling-induced synchronization contrasts other neural networks (e.g., auto-encoders) in that we propose a framework of neural communication among neurons for transmitting information rather than approximating a function that maps the data from high-dimensional space to low-dimensional space (i.e, encoding/decoding).…”

Section: Synchrony As a Mechanism For Controlling Dimensionalitymentioning

confidence: 99%

Electrical coupling controls dimensionality and chaotic firing of inferior olive neurons

et al. 2020

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We previously proposed, on theoretical grounds, that the cerebellum must regulate the dimensionality of its neuronal activity during motor learning and control to cope with the low firing frequency of inferior olive neurons, which form one of two major inputs to the cerebellar cortex. Such dimensionality regulation is possible via modulation of electrical coupling through the gap junctions between inferior olive neurons by inhibitory GABAergic synapses. In addition, we previously showed in simulations that intermediate coupling strengths induce chaotic firing of inferior olive neurons and increase their information carrying capacity. However, there is no in vivo experimental data supporting these two theoretical predictions. Here, we computed the levels of synchrony, dimensionality, and chaos of the inferior olive code by analyzing in vivo recordings of Purkinje cell complex spike activity in three different coupling conditions: carbenoxolone (gap junctions blocker), control, and picrotoxin (GABA-A receptor antagonist). To examine the effect of electrical coupling on dimensionality and chaotic dynamics, we first determined the physiological range of effective coupling strengths between inferior olive neurons in the three conditions using a combination of a biophysical network model of the inferior olive and a novel Bayesian model averaging approach. We found that effective coupling co-varied with synchrony and was inversely related to the dimensionality of inferior olive firing dynamics, as measured via a principal component analysis of the spike trains in each condition. Furthermore, for both the model and the data, we found an inverted U-shaped relationship between coupling strengths and complexity entropy, a measure of chaos for spiking neural data. These results are consistent with our hypothesis according to which electrical coupling regulates the dimensionality and the complexity in the inferior olive neurons in order to optimize both motor learning and control of high dimensional motor systems by the cerebellum.

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“…A second possibility is that the differentiation of iPCs is dictated by the timing of the establishment of the cerebellar circuitry. We speculate that efficient regeneration is possible at P1 because PCs still have an immature morphology and integration into the cerebellar circuitry, whereas at later stages the parallel fibers (axons of granule cells) synapse with PCs and climbing fibers (axons of the inferior olive neurons) refine their synapses and both cells promote PC maturation ( Good et al, 2017 ; Hoxha et al, 2017 ). Thus, maturation and integration of a newly generated PC into the cerebellar circuitry might not be efficient or possible after P5.…”

Section: Resultsmentioning

confidence: 99%

Age-dependent dormant resident progenitors are stimulated by injury to regenerate Purkinje neurons

Bayın

Wojcinski

Mourton

et al. 2018

eLife

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Outside of the neurogenic niches of the brain, postmitotic neurons have not been found to undergo efficient regeneration. We demonstrate that mouse Purkinje cells (PCs), which are born at midgestation and are crucial for development and function of cerebellar circuits, are rapidly and fully regenerated following their ablation at birth. New PCs are produced from immature FOXP2+ Purkinje cell precursors (iPCs) that are able to enter the cell cycle and support normal cerebellum development. The number of iPCs and their regenerative capacity, however, diminish soon after birth and consequently PCs are poorly replenished when ablated at postnatal day five. Nevertheless, the PC-depleted cerebella reach a normal size by increasing cell size, but scaling of neuron types is disrupted and cerebellar function is impaired. Our findings provide a new paradigm in the field of neuron regeneration by identifying a population of immature neurons that buffers against perinatal brain injury in a stage-dependent process.

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Maturation of Cerebellar Purkinje Cell Population Activity during Postnatal Refinement of Climbing Fiber Network

Cited by 23 publications

References 32 publications

Developmental synapse remodeling in the cerebellum and visual thalamus

Developmental synapse remodeling in the cerebellum and visual thalamus

Electrical coupling controls dimensionality and chaotic firing of inferior olive neurons

Age-dependent dormant resident progenitors are stimulated by injury to regenerate Purkinje neurons

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