Golgi tendon organs and Pacinian corpuscles are peripheral mechanoreceptors that disappear after denervation during a critical period in early postnatal development. Even if regeneration is allowed to occur, Golgi tendon organs do not reform, and the reformation of Pacinian corpuscles is greatly impaired. The sensory nerve terminals of both types of mechanoreceptors are closely associated with Schwann cells. Here we investigate the changes in the Schwann cells found in Golgi tendon organs and Pacinian corpuscles after nerve resection in the early neonatal period. We report that denervation induces the apoptotic death of these Schwann cells and that this apoptosis can be prevented by administration of a soluble form of neuregulin, glial growth factor 2. Schwann cells associated with these mechanoreceptors are immunoreactive for the neuregulin receptors erbB2, erbB3, and erbB4, and the sensory nerve terminals are immunoreactive for neuregulin. Our results suggest that Schwann cells in developing sensory end organs are trophically dependent on sensory axon terminals and that an axon-derived neuregulin mediates this trophic interaction. The denervation-induced death of mechanoreceptor Schwann cells is correlated with deficiencies in the re-establishment of these sensory end organs by regenerating axons.

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Invertebrates have proved to be important experimental systems for examining questions related to growth cone navigation and nerve formation, in large part because of their simpler nervous systems. However, such apparent simplicity can be deceiving because the final stereotyped patterns may be the result of multiple developmental mechanisms and not necessarily the sole consequence of the pathway choices of individual growth cones. We have examined the normal sequence of events that are involved in the formation of the major peripheral nerves in leech embryos by employing (1) an antibody directed against acetylated tubulin to label neurons growing out from the central nervous system, (2) the Lan3-2 antibody to label a specific population of peripheral neurons growing into the central nervous system, and (3) intracellular dye filling of single cells. We found that the mature pattern of nerves was characterized by a pair of large nerve roots, each of which branched into two major tracts. The earliest axonal projections did not, however, establish this pattern definitively. Rather, each of the four nerves initially formed as discrete, roughly parallel tracts without bifurcation, with the final branching pattern of the nerve roots being generated by a secondary condensation. In addition, we found that some of the nerves were pioneered in different ways and by different groups of neurons. One of the nerves was established by central neurons growing peripherally, another by peripheral neurons growing centrally. These results suggest that the formation of common nerves and neuronal pathfinding in the leech involves multiple sets of growth cone guidance strategies and morphogenetic mechanisms that belie its apparent simplicity.

Competition among the several motor axons transiently innervating neonatal muscle fibers results in an increasing disparity in the quantal content and synaptic territory of each competitor, culminating in the permanent loss of all but one axon from neuromuscular junctions. We asked whether differences in the probability of neurotransmitter release also contribute to the increasing disparity in quantal content among competing inputs, and when in the process of competition changes in release probability become apparent. To address these questions, intracellular recordings were made from dually innervated neonatal mouse soleus muscle fibers, and quantal content and paired-pulse facilitation were evaluated for each input. At short interpulse intervals, paired-pulse facilitation was significantly higher for the weaker input with the smaller quantal content than the stronger input with the larger quantal content. Because neurotransmitter release probability across all release sites is inversely related to the extent of facilitation observed after paired-pulse stimulation, this result suggests that release probability is lower for weak compared with strong inputs innervating the same junction. A disparity in the probability of neurotransmitter release thus contributes to the disparity in quantal content that occurs during synaptic competition. Together, this work suggests that an input incapable of sustaining a high release probability may be at a competitive disadvantage for synaptic maintenance.

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