Scientific Understanding of Consciousness
Motor Tasks via Brainstem Nucleus
Nature 508, 351–356 (17 April 2014)
Brainstem nucleus MdV mediates skilled forelimb motor tasks
Maria Soledad Esposito, Paolo Capelli & Silvia Arber
Biozentrum, Department of Cell Biology, University of Basel, Basel 4056, Switzerland
Friedrich Miescher Institute for Biomedical Research, Basel 4058, Switzerland
Translating the behavioural output of the nervous system into movement involves interaction between brain and spinal cord. The brainstem provides an essential bridge between the two structures, but circuit-level organization and function of this intermediary system remain poorly understood. Here we use intersectional virus tracing and genetic strategies in mice to reveal a selective synaptic connectivity matrix between brainstem substructures and functionally distinct spinal motor neurons that regulate limb movement. The brainstem nucleus medullary reticular formation ventral part (MdV) stands out as specifically targeting subpopulations of forelimb-innervating motor neurons. Its glutamatergic premotor neurons receive synaptic input from key upper motor centres and are recruited during motor tasks. Selective neuronal ablation or silencing experiments reveal that MdV is critically important specifically for skilled motor behaviour, including accelerating rotarod and single-food-pellet reaching tasks. Our results indicate that distinct premotor brainstem nuclei access spinal subcircuits to mediate task-specific aspects of motor programs.
Initiation of natural movement depends on the function of descending pathways to the spinal cord. This critical need is strikingly obvious in patients with complete spinal cord injury who lack the ability to move muscles controlled by spinal segments below the lesion, despite the presence of functional circuits in the spinal cord. Descending motor control pathways are at the core of supporting different forms of movement spanning from repetitive basic locomotor tasks such as walking to sophisticated fine motor tasks like object manipulation. Classical studies provide evidence that electrical stimulation of diverse areas in the brainstem can elicit a variety of movement sequences mediated by the reticular formation. However, neuronal subpopulations and descending circuit modules linked to these diverse functions remain largely undefined.
Descending motor pathways with projections to the spinal cord operate in a dual mode of synaptic communication. They can contact spinal interneurons to indirectly influence motor neuron activity, and they can establish direct synaptic connections with motor neurons representing the shortest line of communication to produce motor output. Evolutionary studies on motor cortex connectivity to spinal motor neurons have provided evidence for greater direct cortical input to motor neurons in species with highly skilled motor behaviours, supporting the idea that evolutionary changes in motor neuron access may influence the action task repertoire an animal can perform. In addition, within any mammalian species, forelimbs are superior to hindlimbs in the execution of sophisticated tasks, raising the question of whether interlimb circuitry comparison of descending input from brainstem to motor neurons may reveal differences in connectivity matrices related to function.
Here we use a trans-synaptic virus approach to visualize and compare connectivity patterns of neurons in the brainstem to forelimb- or hindlimb-innervating motor neurons in the mouse spinal cord, revealing striking differences of descending input to distinct spinal motor neurons. The medullary reticular formation ventral part (MdV) is a key brainstem area specifically connecting to a subset of forelimb-innervating spinal motor neurons. We show that MdV neurons receive input from upstream motor control centres and are essential for efficient performance of skilled motor tasks. Our findings provide a circuit- and subpopulation-level connectivity map for descending pathways regulating limb motor control and put forward a model in which distinct brainstem hubs differentially address spinal circuits to control motor actions.
Descending pathways carry motor commands to the spinal cord, linking motor plan to task execution. Our study demonstrates that a larger variety of brainstem nuclei target forelimb than hindlimb motor neurons, correlating with the higher complexity and repertoire of forelimb motor tasks. We demonstrate the involvement of the forelimb-dominated brainstem nucleus MdV in expert performance of a skilled motor subroutine, supporting a model in which distinct brainstem subpopulations control aspects of motor behaviour through their specific targeted spinal subcircuits.
Forelimb-dominated brainstem nuclei show highly selective synaptic interaction matrices with spinal subcircuits, including specific motor neuron pools and spinal interneurons. Our findings agree with the concept that descending pathways to motor neurons operate through a dichotomous circuit connection strategy of both direct and indirect pathways. Direct pathways deliver commands to specific executing motor neuron pools, thus creating bypass circuits that may provide means to disregard the contribution of local spinal circuits often engaged in rhythmic activities. In contrast, indirect motor command pathways contribute to local spinal computation by intersection with spinal microcircuits to enhance or suppress output channels to targeted motor neuron pools. Dichotomy in descending circuit architecture and its possible correlation to sophistication of skilled movement has been most prominently discussed for motor cortical connections to spinal circuits. Especially during challenging forelimb movements such as reaching or object manipulation, electromyographic recordings provide evidence for complex sequences of muscle contractions, and flexible divergent circuit architecture with access to specific motor neuron pools may allow achieving a higher degree of muscle synergies, known to be regulated by descending pathwaysOur study provides important insight into circuit-level mechanisms and anatomical substrates essential to implement task-specific motor subroutines during the execution of a complex motor program.
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