Proper axonal branch growth and targeting are essential for establishing a hard-wired neural circuit. Here, we examined the role of Fibroblast Growth Factor Receptors (FGFRs) in axonal arbor development using loss of function and overexpression genetic analyses within single neurons. We used the invariant synaptic connectivity patterns of Drosophila mechanosensory neurons with their innate cleaning reflex responses as readouts for errors in synaptic targeting and circuit function. FGFR loss of function resulted in a decrease in axonal branch number and lengths, and overexpression of FGFRs resulted in ectopic branches and increased lengths. FGFR mutants produced stereotyped axonal targeting errors. Both loss of function and overexpression of FGFRs within the mechanosensory neuron decreased the animal's frequency of response to mechanosensory stimulation. Our results indicate that FGFRs promote axonal branch growth and proper branch targeting. Disrupting FGFRs results in miswiring and impaired neural circuit function.
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http://dx.doi.org/10.1186/s13041-019-0503-y | DOI Listing |
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Laboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA.
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Otology & Neurotology Group CTS495, Division of Otolaryngology, Department of Surgery, Instituto de Investigación Biosanitaria, Ibs.GRANADA, Granada, Universidad de Granada, Granada, Spain.
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Shenzhen Key Laboratory of Neuroimmunomodulation for Neurological Diseases, Shenzhen-Hong Kong Institute of Brain Science, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.
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School of Stomatology, The First Affiliated Hospital of Harbin Medical University, Harbin Medical University, Harbin, 150000, China.
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View Article and Find Full Text PDFJ Clin Invest
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Department of Neurology, UCSF, San Francisco, United States of America.
NMDA receptor mediated autoimmune encephalitis (NMDAR-AE) frequently results in persistent sensory-motor deficits, especially in children, yet the underlying mechanisms remain unclear. This study investigated the long- term effects of exposure to a patient-derived GluN1-specific monoclonal antibody (mAb) during a critical developmental period (from postnatal day 3 to day 12) in mice. We observed long-lasting sensory-motor deficits characteristic of NMDAR-AE, along with permanent changes in callosal axons within the primary somatosensory cortex (S1) in adulthood, including increased terminal branch complexity.
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