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2.
Nature ; 590(7846): 445-450, 2021 02.
Article in English | MEDLINE | ID: mdl-33408409

ABSTRACT

The brainstem is a key centre in the control of body movements. Although the precise nature of brainstem cell types and circuits that are central to full-body locomotion are becoming known1-5, efforts to understand the neuronal underpinnings of skilled forelimb movements have focused predominantly on supra-brainstem centres and the spinal cord6-12. Here we define the logic of a functional map for skilled forelimb movements within the lateral rostral medulla (latRM) of the brainstem. Using in vivo electrophysiology in freely moving mice, we reveal a neuronal code with tuning of latRM populations to distinct forelimb actions. These include reaching and food handling, both of which are impaired by perturbation of excitatory latRM neurons. Through the combinatorial use of genetics and viral tracing, we demonstrate that excitatory latRM neurons segregate into distinct populations by axonal target, and act through the differential recruitment of intra-brainstem and spinal circuits. Investigating the behavioural potential of projection-stratified latRM populations, we find that the optogenetic stimulation of these populations can elicit diverse forelimb movements, with each behaviour stably expressed by individual mice. In summary, projection-stratified brainstem populations encode action phases and together serve as putative building blocks for regulating key features of complex forelimb movements, identifying substrates of the brainstem for skilled forelimb behaviours.


Subject(s)
Brain Stem/cytology , Brain Stem/physiology , Forelimb/innervation , Forelimb/physiology , Motor Skills/physiology , Neural Pathways , Animals , Female , Male , Medulla Oblongata/cytology , Medulla Oblongata/physiology , Mice , Movement
3.
Annu Rev Neurosci ; 42: 485-504, 2019 07 08.
Article in English | MEDLINE | ID: mdl-31283898

ABSTRACT

Neuronal circuits that regulate movement are distributed throughout the nervous system. The brainstem is an important interface between upper motor centers involved in action planning and circuits in the spinal cord ultimately leading to execution of body movements. Here we focus on recent work using genetic and viral entry points to reveal the identity of functionally dedicated and frequently spatially intermingled brainstem populations essential for action diversification, a general principle conserved throughout evolution. Brainstem circuits with distinct organization and function control skilled forelimb behavior, orofacial movements, and locomotion. They convey regulatory parameters to motor output structures and collaborate in the construction of complex natural motor behaviors. Functionally tuned brainstem neurons for different actions serve as important integrators of synaptic inputs from upstream centers, including the basal ganglia and cortex, to regulate and modulate behavioral function in different contexts.


Subject(s)
Brain Stem/physiology , Motor Neurons/physiology , Movement/physiology , Spinal Cord/physiology , Animals , Humans , Locomotion/physiology , Neural Pathways/physiology
4.
Neuron ; 100(2): 361-374, 2018 10 24.
Article in English | MEDLINE | ID: mdl-30359602

ABSTRACT

Locomotion is regulated by distributed circuits and achieved by the concerted activation of body musculature. While the basic properties of executive circuits in the spinal cord are fairly well understood, the precise mechanisms by which the brain impacts locomotion are much less clear. This Review discusses recent work unraveling the cellular identity, connectivity, and function of supraspinal circuits. We focus on their involvement in the regulation of the different phases of locomotion and their interaction with spinal circuits. Dedicated neuronal populations in the brainstem carry locomotor instructions, including initiation, speed, and termination. To align locomotion with behavioral needs, brainstem output structures are recruited by midbrain and forebrain circuits that compute and infer volitional, innate, and context-dependent locomotor properties. We conclude that the emerging logic of supraspinal circuit organization helps to understand how locomotor programs from exploration to hunting and escape are regulated by the brain.


Subject(s)
Brain/physiology , Locomotion/physiology , Neural Pathways/physiology , Spinal Cord/physiology , Animals , Humans
5.
Neuron ; 92(5): 1063-1078, 2016 Dec 07.
Article in English | MEDLINE | ID: mdl-27866798

ABSTRACT

Locomotion is an essential animal behavior used for translocation. The spinal cord acts as key executing center, but how it coordinates many body parts located across distance remains poorly understood. Here we employed mouse genetic and viral approaches to reveal organizational principles of long-projecting spinal circuits and their role in quadrupedal locomotion. Using neurotransmitter identity, developmental origin, and projection patterns as criteria, we uncover that spinal segments controlling forelimbs and hindlimbs are bidirectionally connected by symmetrically organized direct synaptic pathways that encompass multiple genetically tractable neuronal subpopulations. We demonstrate that selective ablation of descending spinal neurons linking cervical to lumbar segments impairs coherent locomotion, by reducing postural stability and speed during exploratory locomotion, as well as perturbing interlimb coordination during reinforced high-speed stepping. Together, our results implicate a highly organized long-distance projection system of spinal origin in the control of postural body stabilization and reliability during quadrupedal locomotion.


Subject(s)
Commissural Interneurons/physiology , Gait/physiology , Locomotion/physiology , Neurons/physiology , Postural Balance/physiology , Spinal Cord/physiology , Animals , Cervical Vertebrae , Forelimb , Hindlimb , Lumbar Vertebrae , Mice , Neurons/metabolism , Spinal Cord/cytology , Vesicular Glutamate Transport Protein 2/metabolism , Vesicular Inhibitory Amino Acid Transport Proteins/metabolism
6.
BMC Biol ; 10: 104, 2012 Dec 18.
Article in English | MEDLINE | ID: mdl-23249484

ABSTRACT

BACKGROUND: Males and females differ in many ways and might present different opportunities and challenges to their parasites. In the same way that parasites adapt to the most common host type, they may adapt to the characteristics of the host sex they encounter most often. To explore this hypothesis, we characterized host sex-specific effects of the parasite Pasteuria ramosa, a bacterium evolving in naturally, strongly, female-biased populations of its host Daphnia magna. RESULTS: We show that the parasite proliferates more successfully in female hosts than in male hosts, even though males and females are genetically identical. In addition, when exposure occurred when hosts expressed a sexual dimorphism, females were more infected. In both host sexes, the parasite causes a similar reduction in longevity and leads to some level of castration. However, only in females does parasite-induced castration result in the gigantism that increases the carrying capacity for the proliferating parasite. CONCLUSIONS: We show that mature male and female Daphnia represent different environments and reveal one parasite-induced symptom (host castration), which leads to increased carrying capacity for parasite proliferation in female but not male hosts. We propose that parasite induced host castration is a property of parasites that evolved as an adaptation to specifically exploit female hosts.


Subject(s)
Daphnia/microbiology , Daphnia/parasitology , Host-Parasite Interactions/physiology , Parasites/growth & development , Pasteuria/growth & development , Sex Characteristics , Animals , Bias , Cell Count , Daphnia/anatomy & histology , Female , Male , Spermatozoa/cytology , Spermatozoa/microbiology , Spermatozoa/parasitology , Spores, Bacterial/growth & development , Survival Analysis
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