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Specificity of sensory-motor connections encoded by Sema3e-Plxnd1 recognition.

Nature | Jun 11, 2009

http://www.ncbi.nlm.nih.gov/pubmed/19421194

Spinal reflexes are mediated by synaptic connections between sensory afferents and motor neurons. The organization of these circuits shows several levels of specificity. Only certain classes of proprioceptive sensory neurons make direct, monosynaptic connections with motor neurons. Those that do are bound by rules of motor pool specificity: they form strong connections with motor neurons supplying the same muscle, but avoid motor pools supplying antagonistic muscles. This pattern of connectivity is initially accurate and is maintained in the absence of activity, implying that wiring specificity relies on the matching of recognition molecules on the surface of sensory and motor neurons. However, determinants of fine synaptic specificity here, as in most regions of the central nervous system, have yet to be defined. To address the origins of synaptic specificity in these reflex circuits we have used molecular genetic methods to manipulate recognition proteins expressed by subsets of sensory and motor neurons. We show here that a recognition system involving expression of the class 3 semaphorin Sema3e by selected motor neuron pools, and its high-affinity receptor plexin D1 (Plxnd1) by proprioceptive sensory neurons, is a critical determinant of synaptic specificity in sensory-motor circuits in mice. Changing the profile of Sema3e-Plxnd1 signalling in sensory or motor neurons results in functional and anatomical rewiring of monosynaptic connections, but does not alter motor pool specificity. Our findings indicate that patterns of monosynaptic connectivity in this prototypic central nervous system circuit are constructed through a recognition program based on repellent signalling.

Pubmed ID: 19421194 RIS Download

Mesh terms: Animals | Cell Adhesion Molecules, Neuronal | Glycoproteins | Membrane Glycoproteins | Membrane Proteins | Mice | Models, Neurological | Motor Neurons | Muscle, Skeletal | Nerve Tissue Proteins | Neural Pathways | Proprioception | Reflex, Monosynaptic | Sensory Receptor Cells | Skin | Synapses

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Associated grants

  • Agency: NINDS NIH HHS, Id: R01 NS065048
  • Agency: NINDS NIH HHS, Id: R01 NS065048-01
  • Agency: NINDS NIH HHS, Id: R01NS065048
  • Agency: Howard Hughes Medical Institute, Id:
  • Agency: Wellcome Trust, Id:

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