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Cell Reports May 2023The cerebellum is essential for motor control and cognitive functioning, engaging in bidirectional communication with the cerebral cortex. The common marmoset, a small...
The cerebellum is essential for motor control and cognitive functioning, engaging in bidirectional communication with the cerebral cortex. The common marmoset, a small non-human primate, offers unique advantages for studying cerebello-cerebral circuits. However, the marmoset cerebellum is not well described in published resources. In this study, we present a comprehensive atlas of the marmoset cerebellum comprising (1) fine-detailed anatomical atlases and surface-analysis tools of the cerebellar cortex based on ultra-high-resolution ex vivo MRI, (2) functional connectivity and gradient patterns of the cerebellar cortex revealed by awake resting-state fMRI, and (3) structural-connectivity mapping of cerebellar nuclei using high-resolution diffusion MRI tractography. The atlas elucidates the anatomical details of the marmoset cerebellum, reveals distinct gradient patterns of intra-cerebellar and cerebello-cerebral functional connectivity, and maps the topological relationship of cerebellar nuclei in cerebello-cerebral circuits. As version 5 of the Marmoset Brain Mapping project, this atlas is publicly available at https://marmosetbrainmapping.org/MBMv5.html.
Topics: Animals; Callithrix; Cerebellum; Magnetic Resonance Imaging; Brain Mapping; Cerebellar Cortex
PubMed: 37163375
DOI: 10.1016/j.celrep.2023.112480 -
Signal Transduction and Targeted Therapy Jun 2022Cerebellar ataxias are characterized by a progressive decline in motor coordination, but the specific output circuits and underlying pathological mechanism remain poorly...
Cerebellar ataxias are characterized by a progressive decline in motor coordination, but the specific output circuits and underlying pathological mechanism remain poorly understood. Through cell-type-specific manipulations, we discovered a novel GABAergic Purkinje cell (PC) circuit in the cerebellar IV/V lobe that projected to CaMKIIα neurons in the fastigial nucleus (FN), which regulated sensorimotor coordination. Furthermore, transcriptomics profiling analysis revealed various cerebellar neuronal identities, and we validated that biorientation defective 1 (BOD1) played an important role in the circuit of IV/V lobe to FN. BOD1 deficit in PCs of IV/V lobe attenuated the excitability and spine density of PCs, accompany with ataxia behaviors. Instead, BOD1 enrichment in PCs of IV/V lobe reversed the hyperexcitability of CaMKIIα neurons in the FN and ameliorated ataxia behaviors in L7-Cre; BOD1 mice. Together, these findings further suggest that specific regulation of the cerebellar IV/V lobe→ FN circuit might provide neuromodulatory targets for the treatment of ataxia behaviors.
Topics: Animals; Ataxia; Cerebellar Nuclei; Mice; Neurons; Purkinje Cells
PubMed: 35641478
DOI: 10.1038/s41392-022-00989-x -
Neuroscience May 2021In the last 50 years, our vision of the cerebellum has vastly evolved starting with Voogd's (1967) description of extracerebellar projections' terminations and how the... (Review)
Review
In the last 50 years, our vision of the cerebellum has vastly evolved starting with Voogd's (1967) description of extracerebellar projections' terminations and how the projection maps transformed the presumptive homogeneity of the cerebellar cortex into a more complex center subdivided into transverse and longitudinal distinct functional zones. The picture became still more complex with Richard Hawkes and colleagues' (Gravel et al., 1987) discovery of the biochemical heterogeneity of Purkinje cells (PCs), by screening their molecular identities with monoclonal antibodies. Antigens were expressed in a parasagittal pattern with subsets of PCs either possessing or lacking the respective antigens, which divided the cerebellar cortex into precise longitudinal compartments that are congruent with the projection maps. The correlation of these two maps in adult cerebellum shows a perfect matching of developmental mechanisms. This review discusses a series of arguments in favor of the essential role played by PCs in organizing the microzonation of the cerebellum during development (the "matching" hypothesis).
Topics: Antibodies, Monoclonal; Antigens; Cerebellar Cortex; Cerebellum; Purkinje Cells
PubMed: 31982466
DOI: 10.1016/j.neuroscience.2020.01.019 -
Neuron May 2023In this issue of Neuron, Xiao et al. reported that inhibitory and excitatory neurons in the pontine central gray encode and transmit opposite valences of sensory...
In this issue of Neuron, Xiao et al. reported that inhibitory and excitatory neurons in the pontine central gray encode and transmit opposite valences of sensory stimuli through parallel circuits to a distributed brain network.
Topics: Pons; Neurons; Pontine Tegmentum; Cerebellar Nuclei
PubMed: 37141860
DOI: 10.1016/j.neuron.2023.04.009 -
Neuron Apr 2022The cerebellum has long been proposed to play a role in cognitive function, although this has remained controversial. This idea has received renewed support with the... (Review)
Review
The cerebellum has long been proposed to play a role in cognitive function, although this has remained controversial. This idea has received renewed support with the recent discovery that signals associated with reward can be observed in the cerebellar circuitry, particularly in goal-directed learning tasks involving an interplay between the cerebellar cortex, basal ganglia, and cerebral cortex. Remarkably, a wide range of reward contingencies-including reward expectation, delivery, size, and omission-can be encoded by specific circuit elements in a manner that reflects the microzonal organization of the cerebellar cortex. The facts that reward signals have been observed in both the mossy fiber and climbing fiber input pathways to the cerebellar cortex and that their convergence may trigger plasticity in Purkinje cells suggest that these interactions may be crucial for the role of the cerebellar cortex in learned behavior. These findings strengthen the emerging consensus that the cerebellum plays a pivotal role in shaping cognitive processing and suggest that the cerebellum may combine both supervised learning and reinforcement learning to optimize goal-directed action. We make specific predictions about how cerebellar circuits can work in concert with the basal ganglia to guide different stages of learning.
Topics: Basal Ganglia; Cerebellum; Neurons; Purkinje Cells; Reward
PubMed: 35325616
DOI: 10.1016/j.neuron.2022.02.015 -
Cerebellum (London, England) Sep 2012Tight regulation of calcium (Ca(2+)) dynamics is critical for all neurons. Ca(2+) is a major mediator of cellular excitability, synaptic plasticity, and regulation of...
Tight regulation of calcium (Ca(2+)) dynamics is critical for all neurons. Ca(2+) is a major mediator of cellular excitability, synaptic plasticity, and regulation of transcription, amongst others. Recent years have seen major developments in terms of understanding the roles of Ca(2+) signals in the cerebellar circuitry, especially for Purkinje neurons and granule cells. The unique morphology of Purkinje neurons serves as a platform to unravel the secrets of Ca(2+) homeostasis in cerebellar microcircuits. This special issue covers recent advances in Ca(2+) signaling and imaging, and highlights the importance of spatiotemporal compartmentalization underlying Ca(2+) dynamics. Sorting out the pieces of the puzzle of homeostatic regulation of Ca(2+) remains an instrumental step to start rational therapies of Ca(2+) deregulation.
Topics: Action Potentials; Animals; Calcium Signaling; Cerebellar Cortex; Cerebellum; Humans; Models, Neurological; Neurons; Patch-Clamp Techniques; Purkinje Cells
PubMed: 22806980
DOI: 10.1007/s12311-012-0404-4 -
The Journal of Comparative Neurology Jul 2022Diverse neurons in the parabrachial nucleus (PB) communicate with widespread brain regions. Despite evidence linking them to a variety of homeostatic functions, it...
Diverse neurons in the parabrachial nucleus (PB) communicate with widespread brain regions. Despite evidence linking them to a variety of homeostatic functions, it remains difficult to determine which PB neurons influence which functions because their subpopulations intermingle extensively. An improved framework for identifying these intermingled subpopulations would help advance our understanding of neural circuit functions linked to this region. Here, we present the foundation of a developmental-genetic ontology that classifies PB neurons based on their intrinsic, molecular features. By combining transcription factor labeling with Cre fate-mapping, we find that the PB is a blend of two, developmentally distinct macropopulations of glutamatergic neurons. Neurons in the first macropopulation express Lmx1b (and, to a lesser extent, Lmx1a) and are mutually exclusive with those in a second macropopulation, which derive from precursors expressing Atoh1. This second, Atoh1-derived macropopulation includes many Foxp2-expressing neurons, but Foxp2 also identifies a subset of Lmx1b-expressing neurons in the Kölliker-Fuse nucleus (KF) and a population of GABAergic neurons ventrolateral to the PB ("caudal KF"). Immediately ventral to the PB, Phox2b-expressing glutamatergic neurons (some coexpressing Lmx1b) occupy the KF, supratrigeminal nucleus, and reticular formation. We show that this molecular framework organizes subsidiary patterns of adult gene expression (including Satb2, Calca, Grp, and Pdyn) and predicts output projections to the amygdala (Lmx1b), hypothalamus (Atoh1), and hindbrain (Phox2b/Lmx1b). Using this molecular ontology to organize, interpret, and communicate PB-related information could accelerate the translation of experimental findings from animal models to human patients.
Topics: Animals; Brain; GABAergic Neurons; Humans; Hypothalamus; Kolliker-Fuse Nucleus; Parabrachial Nucleus; Pons; Transcription Factors
PubMed: 35134251
DOI: 10.1002/cne.25307 -
Cerebellum (London, England) Dec 2011
Topics: Animals; Cerebellar Nuclei; Cerebellum; Humans; Purkinje Cells; Vestibular Nuclei
PubMed: 21279491
DOI: 10.1007/s12311-010-0245-y -
Frontiers in Neural Circuits 2013In many neuroscience fields, the study of local and global rhythmicity has been receiving increasing attention. These network influences could directly impact on how... (Review)
Review
In many neuroscience fields, the study of local and global rhythmicity has been receiving increasing attention. These network influences could directly impact on how neuronal groups interact together, organizing for different contexts. The cerebellar cortex harbors a variety of such local circuit rhythms, from the rhythms in the cerebellar cortex per se, or those dictated from important afferents. We present here certain cerebellar oscillatory phenomena that have been recorded in rodents and primates. Those take place in a range of frequencies: from the more known oscillations in the 4-25 Hz band, such as the olivocerebellar oscillatory activity and the granule cell layer oscillations, to the more recently reported slow (<1 Hz oscillations), and the fast (>150 Hz) activity in the Purkinje cell layer. Many of these oscillations appear spontaneously in the circuits, and are modulated by behavioral imperatives. We review here how those oscillations are recorded, some of their modulatory mechanisms, and also identify some of the cerebellar nodes where they could interact. A particular emphasis has been placed on how these oscillations could be modulated by movement and certain neuropathological manifestations. Many of those oscillations could have a definite impact on the way information is processed in the cerebellum and how it interacts with other structures in a variety of contexts.
Topics: Action Potentials; Animals; Cerebellar Cortex; Cerebellum; Humans; Nerve Net; Periodicity
PubMed: 23908606
DOI: 10.3389/fncir.2013.00125 -
Current Biology : CB Feb 2022Coordination of bilateral movements is essential for a large variety of animal behaviors. The olivocerebellar system is critical for the control of movement, but its...
Coordination of bilateral movements is essential for a large variety of animal behaviors. The olivocerebellar system is critical for the control of movement, but its role in bilateral coordination has yet to be elucidated. Here, we examined whether Purkinje cells encode and influence synchronicity of left-right whisker movements. We found that complex spike activity is correlated with a prominent left-right symmetry of spontaneous whisker movements within parts, but not all, of Crus1 and Crus2. Optogenetic stimulation of climbing fibers in the areas with high and low correlations resulted in symmetric and asymmetric whisker movements, respectively. Moreover, when simple spike frequency prior to the complex spike was higher, the complex spike-related symmetric whisker protractions were larger. This finding alludes to a role for rebound activity in the cerebellar nuclei, which indeed turned out to be enhanced during symmetric protractions. Tracer injections suggest that regions associated with symmetric whisker movements are anatomically connected to the contralateral cerebellar hemisphere. Together, these data point toward the existence of modules on both sides of the cerebellar cortex that can differentially promote or reduce the symmetry of left and right movements in a context-dependent fashion.
Topics: Action Potentials; Animals; Cerebellum; Movement; Optogenetics; Purkinje Cells; Vibrissae
PubMed: 35016009
DOI: 10.1016/j.cub.2021.12.020