Specificity of sensory–motor connections encoded by Sema3e–Plxnd1 recognition

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Abstract
Reflex circuits are carefully and specifically formed between sensory and motor neurons based on the class of sensory cell and the muscle type innervated by the motor neuron. Pecho-Vrieseling et al. now report that this fine synaptic specificity is mediated by selective expression of Sema3e and PlexinD1 by specific motor and sensory neuron populations, respectively. Signalling cascades activated by these molecular repellents affected not only monosynaptic circuit anatomy, but also circuit function. Reflex circuits are specifically formed between sensory and motor neurons based on the class of sensory cell and the muscle type innervated by the motor neuron. Here, this fine synaptic specificity is found to be mediated by selective expression of the class 3 semaphorin Sema3e and its high-affinity receptor plexin D1 (Plxnd1) by specific motor and sensory neuron populations, respectively. Spinal reflexes are mediated by synaptic connections between sensory afferents and motor neurons1,2,3. The organization of these circuits shows several levels of specificity. Only certain classes of proprioceptive sensory neurons make direct, monosynaptic connections with motor neurons4. 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 muscles1,5,6,7. This pattern of connectivity is initially accurate and is maintained in the absence of activity8, 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.