AUTHOR=Asante Emilia , Hummel Devynn , Gurung Suman , Kassim Yasmin M. , Al-Shakarji Noor , Palaniappan Kannappan , Sittaramane Vinoth , Chandrasekhar Anand 

TITLE=Defective Neuronal Positioning Correlates With Aberrant Motor Circuit Function in Zebrafish

JOURNAL=Frontiers in Neural Circuits

VOLUME=15

YEAR=2021

URL=https://www.frontiersin.org/journals/neural-circuits/articles/10.3389/fncir.2021.690475

DOI=10.3389/fncir.2021.690475

ISSN=1662-5110

ABSTRACT=<p>Precise positioning of neurons resulting from cell division and migration during development is critical for normal brain function. Disruption of neuronal migration can cause a myriad of neurological disorders. To investigate the functional consequences of defective neuronal positioning on circuit function, we studied a zebrafish <italic>frizzled3a</italic> (<italic>fzd3a</italic>) loss-of-function mutant <italic>off-limits</italic> (<italic>olt</italic>) where the facial branchiomotor (FBM) neurons fail to migrate out of their birthplace. A jaw movement assay, which measures the opening of the zebrafish jaw (gape), showed that the frequency of gape events, but not their amplitude, was decreased in <italic>olt</italic> mutants. Consistent with this, a larval feeding assay revealed decreased food intake in <italic>olt</italic> mutants, indicating that the FBM circuit in mutants generates defective functional outputs. We tested various mechanisms that could generate defective functional outputs in mutants. While <italic>fzd3a</italic> is ubiquitously expressed in neural and non-neural tissues, jaw cartilage and muscle developed normally in <italic>olt</italic> mutants, and muscle function also appeared to be unaffected. Although FBM neurons were mispositioned in <italic>olt</italic> mutants, axon pathfinding to jaw muscles was unaffected. Moreover, neuromuscular junctions established by FBM neurons on jaw muscles were similar between wildtype siblings and <italic>olt</italic> mutants. Interestingly, motor axons innervating the interhyoideus jaw muscle were frequently defasciculated in <italic>olt</italic> mutants. Furthermore, GCaMP imaging revealed that mutant FBM neurons were less active than their wildtype counterparts. These data show that aberrant positioning of FBM neurons in <italic>olt</italic> mutants is correlated with subtle defects in fasciculation and neuronal activity, potentially generating defective functional outputs.</p>