Role of PKMz in morphological and synaptic development of optic tectal neurons in Xenopus laevis tadpoles in vivo

Xuefeng Liu
2010
PKMz (Protein Kinase M zeta) is a recently identified isoform of Protein Kinase C. It is persistently active upon synthesis because its sequence resembles the catalytic domain of PKC zeta but lacks the auto-inhibitory regulatory domain. Previous studies found that PKMz is critical for LTP maintenance, as well as learning and memory in the adult rat brain. However, it is not known whether and how it functions in developing neural systems. I have identified endogenous PKMz in Xenopus laevis
more » ... enopus laevis tadpoles brain and found that its expression pattern is temporally and spatially correlated with synaptogenesis and dendritogenesis within tadpole retino-tectal system. By in vivo rapid time-lapse imaging and three-dimensional analysis of dynamic dendritic growth, I find that exogenous expression of PKMz within single neurons stabilizes dendritic filopodia by increasing dendritic filopodial lifetimes and decreasing filopodial additions, eliminations, and motility, whereas long-term in vivo imaging demonstrates restricted expansion of the dendritic arbor. Alternatively, blocking endogenous PKMz activity in individual growing tectal neurons with ZIP (zeta-inhibitory peptide) destabilizes dendritic filopodia and over long periods promotes excessive arbor expansion. Consistent with its established roles in regulating adult glutamatergic synaptic transmission, I also examined role of PKMz in regulating developing synapses, using both immunohistochemistry and in vivo patch clamp recording. Specifically, I find that knocking down endogenous PKMz using a morpholino impairs both transmission and maturation of glutamatergic synapses, and consistently induces promoted dendritic expansion as seen in ZIP treated neurons. The model that PKMz regulates dendritogenesis by regulating glutamatergic synaptic transmission was further investigated using a novel seizure model based on Xenopus tadpoles. I find that PTZ induced seizure activity increases normalized expression level of brain PKMz, which is required for over-stabilization of dendritic fi [...]
doi:10.14288/1.0071337 fatcat:kb564nzolna5lkfofk4ehzs3lu