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Cell Jan 2023The cortex influences movement by widespread top-down projections to many nervous system regions. Skilled forelimb movements require brainstem circuitry in the medulla;...
The cortex influences movement by widespread top-down projections to many nervous system regions. Skilled forelimb movements require brainstem circuitry in the medulla; however, the logic of cortical interactions with these neurons remains unexplored. Here, we reveal a fine-grained anatomical and functional map between anterior cortex (AC) and medulla in mice. Distinct cortical regions generate three-dimensional synaptic columns tiling the lateral medulla, topographically matching the dorso-ventral positions of postsynaptic neurons tuned to distinct forelimb action phases. Although medial AC (MAC) terminates ventrally and connects to forelimb-reaching-tuned neurons and its silencing impairs reaching, lateral AC (LAC) influences dorsally positioned neurons tuned to food handling, and its silencing impairs handling. Cortico-medullary neurons also extend collaterals to other subcortical structures through a segregated channel interaction logic. Our findings reveal a precise alignment between cortical location, its function, and specific forelimb-action-tuned medulla neurons, thereby clarifying interaction principles between these two key structures and beyond.
Topics: Mice; Animals; Movement; Neurons; Forelimb; Brain Stem
PubMed: 36608651
DOI: 10.1016/j.cell.2022.12.009 -
Current Opinion in Genetics &... Aug 2021Mammal forelimbs are highly diverse, ranging from the elongated wing of a bat to the stout limb of the mole. The mammal forelimb has been a long-standing system for the... (Review)
Review
Mammal forelimbs are highly diverse, ranging from the elongated wing of a bat to the stout limb of the mole. The mammal forelimb has been a long-standing system for the study of early developmental patterning, proportional variation, shape change, and the reduction of elements. However, most of this work has been performed in mice, which neglects the wide variation present across mammal forelimbs. This review emphasizes the critical role of non-model systems in limb evo-devo and highlights new emerging models and their potential. We discuss the role of gene networks in limb evolution, and touch on functional analyses that lay the groundwork for further developmental studies. Mammal limb evo-devo is a rich field, and here we aim to synthesize the findings of key recent works and the questions to which they lead.
Topics: Animals; Biological Evolution; Developmental Biology; Forelimb; Mammals; Mice; Phenotype
PubMed: 33684847
DOI: 10.1016/j.gde.2021.01.012 -
Current Biology : CB Jun 2017The evolutionary pressures shaping humans' unique bipedal locomotion have been a focus of research since Darwin, but the origins of humans' economical walking gait and... (Review)
Review
The evolutionary pressures shaping humans' unique bipedal locomotion have been a focus of research since Darwin, but the origins of humans' economical walking gait and endurance running capabilities remain unclear. Here, I review the anatomical and physiological determinants of locomotor economy (e.g., limb length and posture) and endurance (e.g., muscle volume and fiber type) and investigate their development in the hominin fossil record. The earliest hominins were bipedal but retained ape-like features in the hind limb that would have limited their walking economy compared to living humans. Moreover, the evolution of bipedalism and the loss of the forelimbs in weight support and propulsion would have reduced locomotor endurance in the earliest hominins and likely restricted ranging. Australopithecus evinced longer hind limbs, extended limb posture, and a stiff midfoot, suggesting improved, human-like economy, but were likely still limited in their endurance compared to modern humans. The appearance of skeletal traits related to endurance (e.g., larger limb joints, spring-like plantar arch) in Homo was somewhat mosaic, with the full endurance suite apparent only ∼1 million years ago. The development of endurance capabilities in Homo appears to parallel the evolutionary increase in brain size, cognitive sophistication, and metabolic rate.
Topics: Animals; Biological Evolution; Forelimb; Hindlimb; Hominidae; Humans; Locomotion; Muscle Fibers, Skeletal; Physical Endurance; Posture
PubMed: 28633035
DOI: 10.1016/j.cub.2017.05.031 -
Current Biology : CB Nov 2022Food handling offers unique yet largely unexplored opportunities to investigate how cortical activity relates to forelimb movements in a natural, ethologically...
Food handling offers unique yet largely unexplored opportunities to investigate how cortical activity relates to forelimb movements in a natural, ethologically essential, and kinematically rich form of manual dexterity. To determine these relationships, we recorded high-speed (1,000 fps) video and multi-channel electrophysiological cortical spiking activity while mice handled food. The high temporal resolution of the video allowed us to decompose active manipulation ("oromanual") events into characteristic submovements, enabling event-aligned analysis of cortical activity. Activity in forelimb M1 was strongly modulated during food handling, generally higher during oromanual events and lower during holding intervals. Optogenetic silencing and stimulation of forelimb M1 neurons partially affected food-handling movements, exerting suppressive and activating effects, respectively. We also extended the analysis to forelimb S1 and lateral M1, finding broadly similar oromanual-related activity across all three areas. However, each area's activity displayed a distinct timing and phasic/tonic temporal profile, which was further analyzed by non-negative matrix factorization and demonstrated to be attributable to area-specific composition of activity classes. Current or future forelimb position could be accurately predicted from activity in all three regions, indicating that the cortical activity in these areas contains high information content about forelimb movements during food handling. These results thus establish that cortical activity during food handling is manipulation specific, distributed, and broadly similar across multiple sensorimotor areas while also exhibiting area- and submovement-specific relationships with the fast kinematic hallmarks of this natural form of complex free-object-handling manual dexterity.
Topics: Animals; Mice; Forelimb; Movement; Optogenetics; Food; Biomechanical Phenomena
PubMed: 36243014
DOI: 10.1016/j.cub.2022.09.045 -
Journal of Neurotrauma Aug 2022Coordinating the four limbs is critical for terrestrial mammalian locomotion. Thoracic spinal transection abolishes neural communication between the brain and spinal...
Coordinating the four limbs is critical for terrestrial mammalian locomotion. Thoracic spinal transection abolishes neural communication between the brain and spinal networks controlling hindlimb/leg movements. Several studies have shown that animal models of spinal transection (spinalization), such as mice, rats, cats, and dogs recover hindlimb locomotion with the forelimbs stationary or suspended. We know less on the ability to generate quadrupedal locomotion after spinal transection, however. We collected kinematic and electromyography data in four adult cats during quadrupedal locomotion at five treadmill speeds before (intact cats) and after low-thoracic spinal transection (spinal cats). We show that adult spinal cats performed quadrupedal treadmill locomotion and modulated their speed from 0.4 m/sec to 0.8 m/sec but required perineal stimulation. During quadrupedal locomotion, several compensatory strategies occurred, such as postural adjustments of the head and neck and the appearance of new coordination patterns between the forelimbs and hindlimbs, where the hindlimbs took more steps than the forelimbs. We also observed temporal changes, such as shorter forelimb cycle/swing durations and shorter hindlimb cycle/stance durations in the spinal state. Forelimb double support periods occupied a greater proportion of the cycle in the spinal state, and hindlimb stride length was shorter. Coordination between the forelimbs and hindlimbs was weakened and more variable in the spinal state. Changes in muscle activity reflected spatiotemporal changes in the locomotor pattern. Despite important changes in the pattern, our results indicate that biomechanical properties of the musculoskeletal system play an important role in quadrupedal locomotion and offset some of the loss in neural communication between networks controlling the forelimbs and hindlimbs after spinal transection.
Topics: Animals; Biomechanical Phenomena; Cats; Electromyography; Forelimb; Hindlimb; Locomotion; Mammals; Spinal Cord
PubMed: 35343245
DOI: 10.1089/neu.2022.0042 -
Journal of Neurophysiology Feb 2021The mammalian motor cortex is topographically organized into representations of discrete body parts (motor maps). Studies in adult rats using long-duration intracortical...
The mammalian motor cortex is topographically organized into representations of discrete body parts (motor maps). Studies in adult rats using long-duration intracortical microstimulation (LD-ICMS) reveal that forelimb motor cortex is functionally organized into several spatially distinct areas encoding complex, multijoint movement sequences: elevate, advance, grasp, and retract. The topographical arrangement of complex movements during development and the influence of skilled learning are unknown. Here, we determined the emergence and topography of complex forelimb movement representations in rats between () and . We further investigated the expression of the maps for complex movements under conditions of reduced cortical inhibition and whether skilled forelimb motor training could alter their developing topography. We report that simple forelimb movements are first evoked at and are confined to the caudal forelimb area (CFA), whereas complex movements first reliably appear at and are observed in both the caudal and rostral forelimb areas (RFA). During development, the topography of complex movement representations undergoes reorganization with "grasp" and "elevate" movements predominantly observed in the RFA and all four complex movements observed in CFA. Under reduced cortical inhibition, simple and complex movements were first observed in the CFA on and , respectively, and the topography is altered relative to a saline control. Further, skilled motor learning was associated with increases in "grasp" and "retract" representations specific to the trained limb. Our results demonstrate that early-life motor experience during development can modify the topography of complex forelimb movement representations. The motor cortex is topographically organized into maps of different body parts. We used to think that the function of motor cortex was to drive individual muscles, but more recently we have learned that it is also organized to make complex movements. However, the development and plasticity of those complex movements is completely unknown. In this paper, the emergence and topography of complex movement representation, as well as their plasticity during development, is detailed.
Topics: Animals; Evoked Potentials, Motor; Forelimb; Male; Motor Cortex; Motor Skills; Neural Inhibition; Neurogenesis; Neuronal Plasticity; Rats; Rats, Long-Evans
PubMed: 33471611
DOI: 10.1152/jn.00531.2020 -
Seminars in Cell & Developmental Biology Jan 2016The limbs are a significant evolutionary innovation that enabled vertebrates to diversify and colonise new environments. Tetrapods have two pairs of limbs, forelimbs in... (Review)
Review
The limbs are a significant evolutionary innovation that enabled vertebrates to diversify and colonise new environments. Tetrapods have two pairs of limbs, forelimbs in the upper body and hindlimbs in the lower body. The morphologies of the forelimbs and hindlimbs are distinct, reflecting their specific locomotory functions although they share many common signalling networks that regulate their development. The paired appendages in vertebrates form at fixed positions along the rostral-caudal axis and this occurs as a consequence of earlier subdivision of the lateral plate mesoderm (LPM) into regions with distinct limb forming potential. In this review, we discuss the molecular mechanisms that confer a broad region of the flank with limb-forming potential and its subsequent refinement into distinct forelimb-forming, hindlimb-forming and interlimb territories.
Topics: Animals; Body Patterning; Forelimb; Gene Expression Regulation, Developmental; Hindlimb; Humans; Limb Buds; Mesoderm; Transcriptional Activation
PubMed: 26643124
DOI: 10.1016/j.semcdb.2015.11.011 -
Developmental Dynamics : An Official... Sep 2021The vertebrate limb is a dynamic structure which has evolved into many diverse forms to facilitate complex behavioral adaptations. The principle molecular and cellular... (Review)
Review
The vertebrate limb is a dynamic structure which has evolved into many diverse forms to facilitate complex behavioral adaptations. The principle molecular and cellular processes that underlie development of the vertebrate limb are well characterized. However, how these processes are altered to drive differential limb development between vertebrates is less well understood. Several vertebrate models are being utilized to determine the developmental basis of differential limb morphogenesis, though these typically focus on later patterning of the established limb bud and may not represent the complete developmental trajectory. Particularly, heterochronic limb development can occur prior to limb outgrowth and patterning but receives little attention. This review summarizes the genetic regulation of vertebrate forelimb diversity, with particular focus on wing reduction in the flightless emu as a model for examining limb heterochrony. These studies highlight that wing reduction is complex, with heterochronic cellular and genetic events influencing the major stages of limb development. Together, these studies provide a broader picture of how different limb morphologies may be established during development.
Topics: Animals; Dromaiidae; Extremities; Forelimb; Gene Expression Regulation, Developmental; Limb Buds; Vertebrates; Wings, Animal
PubMed: 33368781
DOI: 10.1002/dvdy.288 -
Brain, Behavior and Evolution 2011It is commonly proposed that the number of fibers that do not cross in the optic chiasm (OC) is proportional to the size of the binocular visual field, and that the... (Review)
Review
It is commonly proposed that the number of fibers that do not cross in the optic chiasm (OC) is proportional to the size of the binocular visual field, and that the major advantage of binocular vision is acute depth perception. I present an alternative, an 'eye-forelimb' (EF) hypothesis, suggesting that alterations in the OC influence the length of neural pathways that transmit visual information to motor nuclei and somatosensory areas involved in forelimb coordination. Evolutionary processes resulting in increased ipsilateral retinal projections (IRP) are of adaptive value in animals that regularly use the forelimbs in a frontal position, while evolutionary change towards reduced IRP is of value for animals that mainly use the forelimbs in lateral positions. Primates and cats, to a large extent, use visually guided forelimb maneuvers, and both groups have high proportions of IRP. The fact that vertebrates' IRP arise exclusively from the temporal retina supports the hypothesis, since IRP from the nasal retina would increase the length of neural pathways involved in forelimb coordination. The EF hypothesis offers new perspectives on why a high proportion of IRP among early limbless vertebrates became reduced during the evolution of laterally situated limbs, and why reptiles that lost their limbs (snakes) evolved more IRP. Anatomical, neurophysiological, phylogenetic, ontogenetic and ecological data suggest that mutations changing the proportions of ipsilateral visual connections in the OC may have selective value for EF coordination.
Topics: Animals; Birds; Cats; Eye Movements; Forelimb; Functional Laterality; Humans; Mammals; Optic Chiasm; Psychomotor Performance; Retina; Retinal Ganglion Cells; Vertebrates; Vision, Binocular; Visual Pathways
PubMed: 21791893
DOI: 10.1159/000329257 -
Nature May 2023The hippocampus is a mammalian brain structure that expresses spatial representations and is crucial for navigation. Navigation, in turn, intricately depends on...
The hippocampus is a mammalian brain structure that expresses spatial representations and is crucial for navigation. Navigation, in turn, intricately depends on locomotion; however, current accounts suggest a dissociation between hippocampal spatial representations and the details of locomotor processes. Specifically, the hippocampus is thought to represent mainly higher-order cognitive and locomotor variables such as position, speed and direction of movement, whereas the limb movements that propel the animal can be computed and represented primarily in subcortical circuits, including the spinal cord, brainstem and cerebellum. Whether hippocampal representations are actually decoupled from the detailed structure of locomotor processes remains unknown. To address this question, here we simultaneously monitored hippocampal spatial representations and ongoing limb movements underlying locomotion at fast timescales. We found that the forelimb stepping cycle in freely behaving rats is rhythmic and peaks at around 8 Hz during movement, matching the approximately 8 Hz modulation of hippocampal activity and spatial representations during locomotion. We also discovered precisely timed coordination between the time at which the forelimbs touch the ground ('plant' times of the stepping cycle) and the hippocampal representation of space. Notably, plant times coincide with hippocampal representations that are closest to the actual position of the nose of the rat, whereas between these plant times, the hippocampal representation progresses towards possible future locations. This synchronization was specifically detectable when rats approached spatial decisions. Together, our results reveal a profound and dynamic coordination on a timescale of tens of milliseconds between central cognitive representations and peripheral motor processes. This coordination engages and disengages rapidly in association with cognitive demands and is well suited to support rapid information exchange between cognitive and sensory-motor circuits.
Topics: Animals; Rats; Forelimb; Hippocampus; Locomotion; Spatial Navigation; Decision Making; Time Factors; Cognition; Efferent Pathways
PubMed: 37046088
DOI: 10.1038/s41586-023-05928-6