Red nucleus structure and function: from anatomy to clinical neurosciences

Abstract

The red nucleus (RN) is a large subcortical structure located in the ventral midbrain. Although it originated as a primitive relay between the cerebellum and the spinal cord, during its phylogenesis the RN shows a progressive segregation between a magnocellular part, involved in the rubrospinal system, and a parvocellular part, involved in the olivocerebellar system. Despite exhibiting distinct evolutionary trajectories, these two regions are strictly tied together and play a prominent role in motor and non-motor behavior in different animal species. However, little is known about their function in the human brain. This lack of knowledge may have been conditioned both by the notable differences between human and non-human RN and by inherent difficulties in studying this structure directly in the human brain, leading to a general decrease of interest in the last decades. In the present review, we identify the crucial issues in the current knowledge and summarize the results of several decades of research about the RN, ranging from animal models to human diseases. Connecting the dots between morphology, experimental physiology and neuroimaging, we try to draw a comprehensive overview on RN functional anatomy and bridge the gap between basic and translational research.

What does the mean mean? A simple test for neuroscience

“…Meanwhile, choice information is conveyed most strongly by the reticular part of the substantia nigra (SNr), which is pivotal in reward-seeking and learning [46][47][48]. The fact that the Red Nucleus (RN), which is involved in coordinated paw movement, contains information about both stimulus and choice is also in agreement with previous literature [49,50]. More surprisingly, Inferior Colliculus (IC), which is classically regarded a hub of auditory processing [51], also contains stimulus and choice information, emphasizing the fact that information is widely distributed across cortical areas [14,44,52].…”

What does the mean mean? A simple test for neuroscience

“…Meanwhile, choice information is conveyed most strongly by the reticular part of the substantia nigra (SNr), which is pivotal in reward-seeking and learning [46][47][48]. The fact that the Red Nucleus (RN), which is involved in coordinated paw movement, contains information about both stimulus and choice is also in agreement with previous literature [49,50]. More surprisingly, Inferior Colliculus (IC), which is classically regarded a hub of auditory processing [51], also contains stimulus and choice information, emphasizing the fact that information is widely distributed across cortical areas [14,44,52].…”

BrainSTEM: A single-cell multiresolution fetal brain atlas reveals transcriptomic fidelity of human midbrain cultures

“…2E). Anatomically, these three groups of neurons are in close proximity, supporting the idea that they may originate from a common intermediate progenitor (24). From our inferred lineages, hNProg.DARN then gives rise to hRN and hNProg.DA, the immediate precursor to hDA and hDA.STN (Fig.…”

Brain Microstructure Interrogation by Diffusion Tensor and Kurtosis Imaging in Progressive Supranuclear Palsy Subtypes

“…Associations were observed between the DKI metrics and clinical test scores, with Kmean associated with ocular motor impairment (PSIS) across midbrain regions (substantia nigra, red nucleus) in both PSP-RS and PSP-P and KFA associated with the severity of parkinsonism (MDS-UPDRS III) in PSP-RS and PD across deep GM regions (globus pallidus externus and putamen) and the anterior portion of the corticostriatal tract. Hence, DKI appears to be a sensitive marker of disease severity, and the findings support the role of midbrain nuclei in the fine regulation of eye movements [51,52] and subcortical GM structures in Parkinsonism. The shared findings across PSP variants and PD also imply a common lesional mechanism at the level of these deep GM nuclei.…”

What does the mean mean? A simple test for neuroscience

“…Meanwhile, choice information is conveyed most strongly by the reticular part of the substantia nigra (SNr), which is pivotal in reward-seeking and learning [46][47][48]. The fact that the Red Nucleus (RN), which is involved in coordinated paw movement, contains information about both stimulus and choice is also in agreement with previous literature [49,50]. More surprisingly, Inferior Colliculus (IC), which is classically regarded a hub of auditory processing [51], also contains stimulus and choice information, emphasizing the fact that information is widely distributed across cortical areas [14,44,52].…”

BrainSTEM: A single-cell multiresolution fetal brain atlas reveals transcriptomic fidelity of human midbrain cultures

“…2E). Anatomically, these three groups of neurons are in close proximity, supporting the idea that they may originate from a common intermediate progenitor (24). From our inferred lineages, hNProg.DARN then gives rise to hRN and hNProg.DA, the immediate precursor to hDA and hDA.STN (Fig.…”

Brain Microstructure Interrogation by Diffusion Tensor and Kurtosis Imaging in Progressive Supranuclear Palsy Subtypes

“…Associations were observed between the DKI metrics and clinical test scores, with Kmean associated with ocular motor impairment (PSIS) across midbrain regions (substantia nigra, red nucleus) in both PSP-RS and PSP-P and KFA associated with the severity of parkinsonism (MDS-UPDRS III) in PSP-RS and PD across deep GM regions (globus pallidus externus and putamen) and the anterior portion of the corticostriatal tract. Hence, DKI appears to be a sensitive marker of disease severity, and the findings support the role of midbrain nuclei in the fine regulation of eye movements [51,52] and subcortical GM structures in Parkinsonism. The shared findings across PSP variants and PD also imply a common lesional mechanism at the level of these deep GM nuclei.…”

What does the mean mean? A simple test for neuroscience

“…Meanwhile, choice information is conveyed most strongly by the reticular part of the substantia nigra (SNr), which is pivotal in reward-seeking and learning [46][47][48]. The fact that the Red Nucleus (RN), which is involved in coordinated paw movement, contains information about both stimulus and choice is also in agreement with previous literature [49,50]. More surprisingly, Inferior Colliculus (IC), which is classically regarded a hub of auditory processing [51], also contains stimulus and choice information, emphasizing the fact that information is widely distributed across cortical areas [14,44,52].…”

BrainSTEM: A single-cell multiresolution fetal brain atlas reveals transcriptomic fidelity of human midbrain cultures

“…2E). Anatomically, these three groups of neurons are in close proximity, supporting the idea that they may originate from a common intermediate progenitor (24). From our inferred lineages, hNProg.DARN then gives rise to hRN and hNProg.DA, the immediate precursor to hDA and hDA.STN (Fig.…”

Brain Microstructure Interrogation by Diffusion Tensor and Kurtosis Imaging in Progressive Supranuclear Palsy Subtypes

“…Associations were observed between the DKI metrics and clinical test scores, with Kmean associated with ocular motor impairment (PSIS) across midbrain regions (substantia nigra, red nucleus) in both PSP-RS and PSP-P and KFA associated with the severity of parkinsonism (MDS-UPDRS III) in PSP-RS and PD across deep GM regions (globus pallidus externus and putamen) and the anterior portion of the corticostriatal tract. Hence, DKI appears to be a sensitive marker of disease severity, and the findings support the role of midbrain nuclei in the fine regulation of eye movements [51,52] and subcortical GM structures in Parkinsonism. The shared findings across PSP variants and PD also imply a common lesional mechanism at the level of these deep GM nuclei.…”