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Synaptic plasticity relies on rapid, yet spatially precise signaling to alter synaptic strength. Arc is a brain enriched protein that is rapidly expressed during learning-related behaviors and is essential for regulating metabotropic glutamate receptor-mediated long-term depression (mGluR-LTD). We previously showed that disrupting the ubiquitination capacity of Arc enhances mGluR-LTD; however, the consequences of Arc ubiquitination on other mGluR-mediated signaling events is poorly characterized. Here we find that pharmacological activation of Group I mGluRs with S-3,5-dihydroxyphenylglycine (DHPG) increases Ca2+release from the endoplasmic reticulum (ER). Disrupting Arc ubiquitination on key amino acid residues enhances DHPG-induced ER-mediated Ca2+release. These alterations were observed in all neuronal subregions except secondary branchpoints. Deficits in Arc ubiquitination altered Arc self-assembly and enhanced its interaction with calcium/calmodulin-dependent protein kinase IIb (CaMKIIb) and constitutively active forms of CaMKII in HEK293 cells. Colocalization of Arc and CaMKII was altered in cultured hippocampal neurons, with the notable exception of secondary branchpoints. Finally, disruptions in Arc ubiquitination were found to increase Arc interaction with the integral ER protein Calnexin. These results suggest a previously unknown role for Arc ubiquitination in the fine tuning of ER-mediated Ca2+signaling that may support mGluR-LTD, which in turn, may regulate CaMKII and its interactions with Arc.more » « less
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Parity-time (PT) symmetry was first studied in quantum mechanical systems with a non-Hermitian Hamiltonian whose observables are real-valued. Most existing designs of PT symmetric systems in electronics, optics, and acoustics rely on an exact balance of loss and gain in the media to achieve PT symmetry. However, the dispersive behavior of most loss and gain materials restricts the frequency range where the system is PT symmetric. This makes it challenging to access the exceptional points of the system to observe the PT symmetric transition dynamics. Here, we propose a new path to realize PT symmetric systems based on gyroscopic effects instead of using loss and gain units. We demonstrate that PT symmetry and the occurrence of exceptional points are preserved for inversive, counter-rotating gyroscopic systems even with dispersive sub-units. In a gyroscopic system with two circular rings rotating in opposite directions at the same speed, the spontaneous symmetry breaking across the exceptional points results in a phase transition from a moving maximum deformation location to a motionless maximum point. The motionless maximum point occurs despite the externally imposed rotation of the two rings. The results set the foundation to study nonlinear dispersive physics in PT symmetric systems, including solitary waves and inelastic wave scattering.more » « less
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