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In the vertebrate somatosensory system, peripheral stimuli are conveyed by sensory neurons located within dorsal root ganglia (DRG) that flank the spinal cord. DRG neurons can be grouped into two major classes, those transducing proprioceptive and cutaneous sensory stimuli. Proprioceptive neurons convey information about the state of muscle contraction and limb position, whereas cutaneous neurons mediate a wide range of noxious and innocuous stimuli. The axons of these two sets of sensory neurons initially project along a common pathway in the dorsal roots, but on entering the spinal cord their axons segregate, and they pursue distinct paths to their target zones. The trajectory of proprioceptive sensory neurons is notable in that their axonal shafts and collaterals avoid the superficial dorsal horn as they project to their ventral targets. In contrast, the axons of high-threshold cutaneous afferents project directly into the superficial dorsal horn, where they innervate target neurons.
After group Ia proprioceptive afferent fibers reach the ventral spinal cord, they make the strongest connections with motor neurons supplying the same muscle, whereas much weaker or no connections are made with motor neurons supplying functionally unrelated muscles. The specific connections between Ia proprioceptive afferents and motor neuron pools seem to be formed in an activity-independent manner, suggesting that the specificity is likely to be genetically determined.
We have been trying to understand molecular mechanisms underlying axon guidance of sensory neurons as well as specificity of sensory-motor connections in the mammalian spinal cord.
Figure 1: Proprioceptive and cutaneous sensory axons follow distinct trajectories in the spinal cord.
The corticospinal system is essential for controlling movements that require fine skills and flexibility in humans. It forms the longest axonal trajectory in the mammalian central nervous system (CNS) and the axons need to navigate the entire length of the CNS from their origins in layer V of the cerebral cortex down to the spinal cord. These features make the CST system an attractive model to study the nature of the directional cues involved in such a navigational task. Study of the corticospinal system also has clinical relevance, since the degeneration and synaptic connection defects of corticospinal motor neurons are key components of motor neuron degenerative diseases, including amyotrophic lateral sclerosis (ALS), and spinal cord injury.
Our lab is interested in understanding molecular mechanisms underlying CST axon guidance and connectivity between CSTs and spinal neurons in the spinal cord.
Figure 2: The right spinal cord shows sensory-motor circuitry, and the left spinal cord shows corticospinal circuitry.
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