Developmental neurobiology
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The peripheral somatosensory system overproduces neurons early in development followed by a period of cell death during final target innervation. The decision to survive or die in somatosensory neurons of the dorsal root ganglion (DRG) is mediated by target-derived neurotrophic factors and their cognate receptors. Subsets of peripheral somatosensory neurons can be crudely defined by the neurotrophic receptors that they express: peptidergic nociceptors (TrkA+), nonpeptidergic nociceptors (Ret+), mechanoreceptors (Ret+ or TrkB+), and proprioceptors (TrkC+). ⋯ We find that TrkA+, TrkB+, and TrkC+ sensory neuron subpopulations require p75NTR for survival, but proliferating progenitors do not. These data demonstrate how diverging sensory neurons undergo successive waves of cell death and how p75NTR represses the magnitude, but not developmental window of this culling. © 2018 Wiley Periodicals, Inc. Develop Neurobiol 78: 701-717, 2018.
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Developmental changes that occur in the prefrontal cortex during adolescence alter behavior. These behavioral alterations likely stem from changes in prefrontal cortex neuronal activity, which may depend on the properties and expression of ion channels. Nav1.9 sodium channels conduct a Na+ current that is TTX resistant with a low threshold and noninactivating over time. ⋯ Nav1.9 immunolabeling was present in layer II and V mPFC pyramidal neurons and was more prominent in the neurons of young rats than in the neurons of late adolescent and adult rats. We conclude that Nav1.9 channels are expressed in layer II and V mPFC pyramidal neurons and that Nav1.9 protein expression in the mPFC pyramidal neurons of late adolescent and adult rats is lower than that in the neurons of young rats. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 77: 1371-1384, 2017.
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Protein kinase C gamma (PKCγ) interneurons, located in the superficial spinal (SDH) and medullary dorsal horns (MDH), have been shown to play a critical role in cutaneous mechanical hypersensitivity. However, a thorough characterization of their development in the MDH is lacking. Here, it is shown that the number of PKCγ-ir interneurons changes from postnatal day 3 (P3) to P60 (adult) and such developmental changes differ according to laminae. ⋯ Finally, neonatal capsaicin treatment, which produces a permanent loss of most unmyelinated afferent fibers, has no effect on the development of PKCγ-ir interneurons. Together, the results show that: (i) the expression of PKCγ-ir interneurons in MDH is developmentally regulated with a critical period at P11-P15, (ii) PKCγ-ir interneurons are developmentally heterogeneous, (iii) lamina IIi PKCγ-ir interneurons appear less vulnerable to cell death, and (iv) postnatal maturation of PKCγ-ir interneurons is due to neither neurogenesis, nor neuronal migration, and is independent of C-fiber development. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 102-119, 2017.
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Many lines of evidence indicate that postsynaptic dendritic spines are plastic during development and largely stable in adulthood. It remains unclear to what degree presynaptic axonal terminals undergo changes in the developing and mature cortex. In this study, we examined the formation and elimination of fluorescently-labeled axonal boutons in the living mouse barrel cortex with transcranial two-photon microscopy. ⋯ In adulthood, 80% of axonal boutons persisted over 12 months and enriched sensory experience caused a slight but not significant increase in the turnover of axonal boutons over 2-4 weeks. Thus, similar to postsynaptic dendritic spines, presynaptic axonal boutons show remarkable stability after development ends. This long-term stability of synaptic connections is likely important for reliable sensory processing in the mature somatosensory cortex.
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Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive paralysis due to the selective death of motor neurons of unknown causes. Increasing evidence indicates that Wnt signaling is altered in ALS. In this study, we focused on two non-canonical Wnt signaling components, atypical PKC (aPKC) and a Wnt receptor, Ryk, in a mouse model of ALS, SOD1 (G93A). aPKC mediates Wnt signaling to regulate growth cone guidance, axon differentiation and cell survival. ⋯ These results suggest that aPKC may be sequestered in SOD1 aggregates, impairing its ability to protect motor neurons from death. Ryk expression was also increased in the motor neurons and the white matter in the ventral lumbar spinal cord of mutant SOD1 mice with a peak at early stage. These observations indicate that Wnt/aPKC and Wnt/Ryk signaling are altered in SOD1 (G93A) mice, suggesting that changed Wnt signaling may contribute to neurodegeneration in ALS.