The vertebrate diencephalic A11 system provides the sole dopaminergic innervation of hindbrain and spinal cord and has been implicated in modulation of locomotion and sensory processes. However, the exact contributions of sensory stimuli and motor behavior to A11 dopaminergic activity remain unclear. We recorded cellular calcium activity in four anatomically distinct posterior tubercular A11-type dopaminergic subgroups and two adjacent hypothalamic dopaminergic groups in GCaMP7a-transgenic, semi-restrained zebrafish larvae. Our analyses reveal the contributions of different sensory modalities and motor states to dopaminergic activity. Each posterior tubercular and hypothalamic subgroup showed distinct activity patterns, while activity was synchronous within individual subgroups. Caudal and dorsomedial hypothalamic dopaminergic neurons are activated following vigorous tail movements and stay active for about 10 s, revealing predominantly post-motor activity. In contrast, posterior tubercular dopaminergic neurons are predominantly sensory driven, with subgroups differentially responding to different tactile or visual sensory modalities. In the anterior subgroups, neuronal response magnitudes are tuned to tactile stimulus intensities, revealing features similar to sensory systems. We identify the lateral line system as source for this tactile tuning. In contrast, the posterior subgroup is responsive to distinct moving visual stimuli. Specifically, translational forward stimuli, which may indicate insufficient rheotaxis and drift, induce dopaminergic activity, but backward or rotational stimuli not. The activation of posterior tubercular dopaminergic neurons by sensory stimuli, and their projections onto peripheral mechanosensory systems, suggests a participation of A11-type neurons in the feedback regulation of sensory systems. Together with the adjacent hypothalamic neurons, they may serve to set basic behavioral states.
Different vaccine platforms were developed in 2019 and 2020 to provide immunization for protection against the SARS-CoV-2-caused disease COVID-19. The majority of vaccinated individuals will develop antibodies against SARS-CoV-2. The isotype (subclass) and Fc-glycosylation of IgG antibodies determine their affinity for secondary effector functions. For protein subunit vaccines in COVID-19, the IgG profile of the subclass and glycosylation are unknown. Therefore, we measured the IgG subclass and N-297 Fc glycosylation by ELISA and LC-MS/MS of anti-spike IgG from individuals vaccinated with the Taiwanese protein subunit vaccine Medigen, the mRNA vaccines (BNT, Moderna), and the adenovector Astrazeneca. Samples were taken after the first and second doses. For all vaccine types, the main IgG response was dominated by IgG1 and IgG3 as subclasses. For glycosylation, mRNA vaccines presented with an afucosylation after the first dose and a constant significant higher galactosylation and sialylation than non-mRNA vaccines.
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