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Current Opinion in Neurobiology Dec 2023Corticostriatal pathways are essential for a multitude of motor, sensory, cognitive, and affective functions. They are mediated by cortical pyramidal neurons, roughly... (Review)
Review
Corticostriatal pathways are essential for a multitude of motor, sensory, cognitive, and affective functions. They are mediated by cortical pyramidal neurons, roughly divided into two projection classes: the pyramidal tract (PT) and the intratelencephalic tract (IT). These pathways have been the focus of numerous studies in recent years, revealing their distinct structural and functional properties. Notably, their synaptic connectivity within ipsi- and contralateral cortical and striatal microcircuits is characterized by a high degree of target selectivity, providing a means to regulate the local neuromodulatory landscape in the striatum. Here, we discuss recent findings regarding the functional organization of the PT and IT corticostriatal pathways and its implications for bilateral sensorimotor functions.
Topics: Neurons; Corpus Striatum; Pyramidal Cells; Pyramidal Tracts; Neural Pathways; Cerebral Cortex
PubMed: 37696188
DOI: 10.1016/j.conb.2023.102781 -
International Journal of Molecular... Jan 2022To date, there is no overarching proposition for the ontogenetic-neurobiological basis of self-regulation. This paper suggests that the balanced self-regulatory reaction... (Review)
Review
To date, there is no overarching proposition for the ontogenetic-neurobiological basis of self-regulation. This paper suggests that the balanced self-regulatory reaction of the fetus, newborn and infant is based on a complex mechanism starting from early brainstem development and continuing to progressive control of the cortex over the brainstem. It is suggested that this balance occurs through the synchronous reactivity between the sympathetic and parasympathetic systems, both which originate from the brainstem. The paper presents an evidence-based approach in which molecular excitation-inhibition balance, interchanges between excitatory and inhibitory roles of neurotransmitters as well as cardiovascular and white matter development across gestational ages, are shown to create sympathetic-parasympathetic synchrony, including the postnatal development of electroencephalogram waves and vagal tone. These occur in developmental milestones detectable in the same time windows (sensitive periods of development) within a convergent systematic progress. This ontogenetic stepwise process is termed "the self-regulation clock" and suggest that this clock is located in the largest connection between the brainstem and the cortex, the corticospinal tract. This novel evidence-based new theory paves the way towards more accurate hypotheses and complex studies of self-regulation and its biological basis, as well as pointing to time windows for interventions in preterm infants. The paper also describes the developing indirect signaling between the suprachiasmatic nucleus and the corticospinal tract. Finally, the paper proposes novel hypotheses for molecular, structural and functional investigation of the "clock" circuitry, including its associations with other biological clocks. This complex circuitry is suggested to be responsible for the developing self-regulatory functions and their neurobehavioral correlates.
Topics: Biological Clocks; Cardiovascular System; Electroencephalography; Female; Gestational Age; Humans; Infant; Infant, Newborn; Pregnancy; Pyramidal Tracts; Suprachiasmatic Nucleus
PubMed: 35055184
DOI: 10.3390/ijms23020993 -
The Journal of Neuroscience : the... Oct 2022Forelimb-related areas of the motor cortex communicate directly to downstream areas in the brainstem and spinal cord via axons that project to and through the pyramidal...
Forelimb-related areas of the motor cortex communicate directly to downstream areas in the brainstem and spinal cord via axons that project to and through the pyramidal tract (PT). To better understand the diversity of the brainstem branching patterns of these pyramidal tract projections, we used MAPseq, a molecular barcode technique for population-scale sampling with single-axon resolution. In experiments using mice of both sexes, we first confirmed prior results demonstrating the basic efficacy of axonal barcode identification of primary motor cortex (M1) PT-type axons, including corticobulbar (CBULB) and corticospinal (CSPI) subclasses. We then used multiplexed MAPseq to analyze projections from M1 and M2 (caudal and rostral forelimb areas). The four basic axon subclasses comprising these projections (M1-CSPI, M1-CBULB, M2-CSPI, M2-CBULB) showed a complex mix of differences and similarities in their brainstem projection profiles. This included relatively abundant branching by all classes in the dorsal midbrain, by M2 subclasses in the pons, and by CSPI subclasses in the dorsal medulla. Cluster analysis showed graded distributions of the basic subclasses within the PT class. Clusters were of diversely mixed subclass composition and showed distinct rostrocaudal and/or dorsomedial projection biases. Exemplifying these patterns was a subcluster likely enriched in corticocuneate branches. Overall, the results indicate high yet systematic PT axon diversity at the level of brainstem branching patterns; projections of M1 and M2 appear qualitatively similar, yet with quantitative differences in subclasses and clusters. Axons of the PT class of cortical projection neurons, which includes corticospinal and corticobulbar neurons, anatomically link motor cortex to brainstem and spinal cord circuits. Both of these subclasses can form branches to brainstem destinations along the way, but the extent and diversity of these branching patterns is incompletely understood. Here, we used MAPseq to tag PT axons with individual molecular barcodes for high-throughput quantification of branching patterns across the brainstem. The results reveal diverse, complex, yet systematic branching patterns of corticospinal and corticobulbar neurons arising from two motor cortex areas, M1 and M2.
Topics: Female; Male; Mice; Animals; Pyramidal Tracts; Axons; Forelimb; Motor Cortex; Upper Extremity
PubMed: 36414009
DOI: 10.1523/JNEUROSCI.1062-22.2022 -
Deutsches Arzteblatt International Mar 2022
Topics: Humans; Magnetic Resonance Imaging; Pyramidal Tracts; Wallerian Degeneration
PubMed: 35535722
DOI: 10.3238/arztebl.m2022.0013 -
Human Brain Mapping Sep 2017Measures from diffusion MRI have been used to characterize the corticospinal tract in chronic stroke. However, diffusivity can be influenced by partial volume effects...
Measures from diffusion MRI have been used to characterize the corticospinal tract in chronic stroke. However, diffusivity can be influenced by partial volume effects from free-water, region of interest placement, and lesion masking. We collected diffusion MRI from a cohort of chronic stroke patients and controls and used a bitensor model to calculate free-water corrected fractional anisotropy (FA ) and free water (FW) in the primary motor corticospinal tract (M1-CST) and the dorsal premotor corticospinal tract (PMd-CST). Region of interest analyses and whole-tract slice-by-slice analyses were used to assess between-group differences in FA and FW in each tract. Correlations between FA and FW and grip strength were also examined. Following lesion masking and correction for multiple comparisons, relative increases in FW were found for the stroke group in large portions of the M1-CST and PMd-CST in the lesioned hemisphere. FW in cortical regions was the strongest predictor of grip strength in the stroke group. Our findings also demonstrated that FA is sensitive to the direct effects of the lesion itself, thus after controlling for the lesion, differences in FA in nonlesioned tissue were small and generally similar between hemispheres and groups. Our observations suggest that FW may be a robust biological measurement that can be used to assess microstructure in residual white matter after stroke. Hum Brain Mapp 38:4546-4562, 2017. © 2017 Wiley Periodicals, Inc.
Topics: Adult; Aged; Aged, 80 and over; Body Water; Brain Ischemia; Chronic Disease; Diffusion Magnetic Resonance Imaging; Female; Hand Strength; Humans; Male; Middle Aged; Motor Cortex; Pyramidal Tracts; Stroke; White Matter
PubMed: 28590584
DOI: 10.1002/hbm.23681 -
Cytometry. Part a : the Journal of the... Sep 2020The submission describes in the form of a communication recent experiences with a promising new therapeutic approach for amyotrophic lateral sclerosis (ALS). This...
The submission describes in the form of a communication recent experiences with a promising new therapeutic approach for amyotrophic lateral sclerosis (ALS). This approach is based on imaging cycler microscopy that led to the discovery of ALS specific cells in the blood, which invade the pyramidal system (lateral corticospinal tract) of ALS patients, where they compress motor axons. The depletion of these cells leads to remission of clinical symptoms and demonstrates the important role of these cells in ALS. The therapy will be offered to ALS patients in licensed and certified centers (in progress). © 2020 International Society for Advancement of Cytometry.
Topics: Amyotrophic Lateral Sclerosis; Humans; Microscopy; Pyramidal Tracts
PubMed: 32510815
DOI: 10.1002/cyto.a.24039 -
Cerebral Cortex (New York, N.Y. : 1991) May 2020Anatomical studies report a large proportion of fine myelinated fibers in the primate pyramidal tract (PT), while very few PT neurons (PTNs) with slow conduction...
Anatomical studies report a large proportion of fine myelinated fibers in the primate pyramidal tract (PT), while very few PT neurons (PTNs) with slow conduction velocities (CV) (<~10 m/s) are reported electrophysiologically. This discrepancy might reflect recording bias toward fast PTNs or prevention of antidromic invasion by recurrent inhibition (RI) of slow PTNs from faster axons. We investigated these factors in recordings made with a polyprobe (32 closely-spaced contacts) from motor cortex of anesthetized rats (n = 2) and macaques (n = 3), concentrating our search on PTNs with long antidromic latencies (ADLs). We identified 21 rat PTNs with ADLs >2.6 ms and estimated CV 3-8 m/s, and 67 macaque PTNs (>3.9 ms, CV 6-12 m/s). Spikes of most slow PTNs were small and present on only some recording contacts, while spikes from simultaneously recorded fast-conducting PTNs were large and appeared on all contacts. Antidromic thresholds were similar for fast and slow PTNS, while spike duration was considerably longer in slow PTNs. Most slow PTNs showed no signs of failure to respond antidromically. A number of tests, including intracortical microinjection of bicuculline (GABAA antagonist), failed to provide any evidence that RI prevented antidromic invasion of slow PTNs. Our results suggest that recording bias is the main reason why previous studies were dominated by fast PTNs.
Topics: Animals; Bicuculline; GABA-A Receptor Antagonists; Macaca; Motor Cortex; Neural Conduction; Neural Inhibition; Neurons; Pyramidal Tracts; Rats
PubMed: 32026928
DOI: 10.1093/cercor/bhz318 -
Developmental Medicine and Child... Dec 2017In maturity, motor skills depend on the corticospinal tract (CST) and brainstem pathways that together synapse on interneurons and motoneurons in the spinal cord.... (Review)
Review
UNLABELLED
In maturity, motor skills depend on the corticospinal tract (CST) and brainstem pathways that together synapse on interneurons and motoneurons in the spinal cord. Descending signals to spinal neurons that mediate voluntary control can be distinguished from peripheral sensory signals, primarily for feedback control. These motor system circuits depend initially on developmental genetic mechanisms to establish their connections and neural activity- and use-dependent synaptic refinement during the early postnatal period to enable motor skills to develop. In this review we consider four key activity-dependent developmental mechanisms that provide insights into how the motor systems establish the proper connections for skilled movement control and how the same mechanisms also inform the mechanisms of motor impairments and developmental plasticity after corticospinal system injury: (1) synaptic competition between the CSTs from each hemisphere; (2) interactions between the CST and spinal cord neurons; (3) synaptic competition between the CST and proprioceptive sensory fibres; and (4) interactions between the developing corticospinal motor system and the rubrospinal tract. Our findings suggest that the corticospinal motor system effectively 'oversees' development of its subcortical targets through synaptic competition and trophic-like interactions and this has important implications for motor impairments after perinatal cortical stroke.
WHAT THIS PAPER ADDS
Neural activity-dependent processes inform the brain and spinal cord response to injury. The corticospinal motor system may 'oversee' development of its downstream subcortical targets through activity, trophic-like interactions, and synaptic competition.
Topics: Animals; Brain; Humans; Motor Cortex; Neuronal Plasticity; Pyramidal Tracts
PubMed: 28972274
DOI: 10.1111/dmcn.13581 -
Brain : a Journal of Neurology May 2023We review the spatial organization of corticospinal outputs from different cortical areas and how this reflects the varied functions mediated by the corticospinal tract.... (Review)
Review
We review the spatial organization of corticospinal outputs from different cortical areas and how this reflects the varied functions mediated by the corticospinal tract. A long-standing question is whether the primate corticospinal tract shows somatotopical organization. Although this has been clearly demonstrated for corticofugal outputs passing through the internal capsule and cerebral peduncle, there is accumulating evidence against somatotopy in the pyramidal tract in the lower brainstem and in the spinal course of the corticospinal tract. Answering the question on somatotopy has important consequences for understanding the effects of incomplete spinal cord injury. Our recent study in the macaque monkey, using high-resolution dextran tracers, demonstrated a great deal of intermingling of fibres originating from primary motor cortex arm/hand, shoulder and leg areas. We quantified the distribution of fibres belonging to these different projections and found no significant difference in their distribution across different subsectors of the pyramidal tract or lateral corticospinal tract, arguing against somatotopy. We further demonstrated intermingling with corticospinal outputs derived from premotor and supplementary motor arm areas. We present new evidence against somatotopy for corticospinal projections from rostral and caudal cingulate motor areas and from somatosensory areas of the parietal cortex. In the pyramidal tract and lateral corticospinal tract, fibres from the cingulate motor areas overlap with each other. Fibres from the primary somatosensory cortex arm area completely overlap those from the leg area. There is also substantial overlap of both these outputs with those from posterior parietal sensorimotor areas. We argue that the extensive intermingling of corticospinal outputs from so many different cortical regions must represent an organizational principle, closely related to its mediation of many different functions and its large range of fibre diameters. The motor sequelae of incomplete spinal injury, such as central cord syndrome and 'cruciate paralysis', include much greater deficits in upper than in lower limb movement. Current teaching and text book explanations of these symptoms are still based on a supposed corticospinal somatotopy or 'lamination', with greater vulnerability of arm and hand versus leg fibres. We suggest that such explanations should now be finally abandoned. Instead, the clinical and neurobiological implications of the complex organization of the corticospinal tract need now to be taken into consideration. This leads us to consider the evidence for a greater relative influence of the corticospinal tract on upper versus lower limb movements, the former best characterized by skilled hand and digit movements.
Topics: Animals; Pyramidal Tracts; Motor Cortex; Hand; Spinal Cord Injuries; Primates
PubMed: 36575147
DOI: 10.1093/brain/awac496 -
Science Advances Sep 2022Restoring limb movements after central nervous system injury remains a substantial challenge. Recent studies proved that crossing nerve transfer surgery could rebuild...
Restoring limb movements after central nervous system injury remains a substantial challenge. Recent studies proved that crossing nerve transfer surgery could rebuild physiological connectivity between the contralesional cortex and the paralyzed arm to compensate for the lost function after brain injury. However, the neural mechanism by which this surgery mediates motor recovery remains still unclear. Here, using a clinical mouse model, we showed that this surgery can restore skilled forelimb function in adult mice with unilateral cortical lesion by inducing cortical remapping and promoting corticospinal tract sprouting. After reestablishing the ipsilateral descending pathway, resecting of the artificially rebuilt peripheral nerve did not affect motor improvements. Furthermore, retaining the sensory afferent, but not the motor efferent, of the transferred nerve was sufficient for inducing brain remapping and facilitating motor restoration. Thus, our results demonstrate that surgically rebuilt sensory input triggers neural plasticity for accelerating motor recovery, which provides an approach for treating central nervous system injuries.
Topics: Animals; Brain Injuries; Forelimb; Mice; Nerve Transfer; Neuronal Plasticity; Pyramidal Tracts
PubMed: 36044580
DOI: 10.1126/sciadv.abn5899