Behavioral control through the direct, focal silencing of neuronal activity.

The ability to optically stimulate and inhibit neurons has revolutionized neuroscience research. Here, we present a direct, potent, user-friendly chemical approach for optically silencing neurons. We have rendered saxitoxin (STX), a naturally occurring paralytic agent, transiently inert through chemical protection with a previously undisclosed nitrobenzyl-derived photocleavable group. Exposing the caged toxin, STX-bpc, to a brief (5 ms) pulse of light effects rapid release of a potent STX derivative and transient, spatially precise blockade of voltage-gated sodium channels (NaVs). We demonstrate the efficacy of STX-bpc for parametrically manipulating action potentials in mammalian neurons and brain slice. Additionally, we show the effectiveness of this reagent for silencing neural activity by dissecting sensory-evoked swimming in larval zebrafish. Photo-uncaging of STX-bpc is a straightforward method for non-invasive, reversible, spatiotemporally precise neural silencing without the need for genetic access, thus removing barriers for comparative research.

Planned Out-of-Hospital Birth as a Risk Factor for Nonreceipt of Hepatitis B Immunization.

BACKGROUND: The hepatitis B vaccine (HBV) is recommended at birth to prevent perinatal hepatitis B transmission; however, many newborns still do not receive HBV. The extent to which planned out-of-hospital births, which have increased over the past decade, are associated with nonreceipt of the HBV birth dose is unknown. The purpose of this study was to determine whether a planned out-of-hospital birth location is associated with the nonreceipt of the HBV birth dose. METHODS: We performed a retrospective cohort study of all births from 2007 to 2019 recorded in the Colorado birth registry. χ2 analyses were used to compare maternal demographics by birth location. Univariate and multiple logistic regression were used to evaluate the association of birth location with nonreceipt of the HBV birth dose. RESULTS: In total 1.5% of neonates born in freestanding birth centers and 0.1% of neonates born at a planned home birth received HBV compared to 76.3% of neonates born in a hospital location. After adjusting for confounders, this translated to a large increase in the odds of not receiving HBV compared to in-hospital births [freestanding birth center (aodds ratio (aOR): 172.98, 95% confidence interval (CI): 136.98-219.88); planned home birth (aOR: 502.05, 95% CI: 363.04-694.29)]. Additionally, older maternal age, White/non-Hispanic race and ethnicity, higher income, and private or no insurance were associated with nonreceipt of the HBV birth dose. CONCLUSIONS: Planned out-of-hospital birth is a risk factor for nonreceipt of the HBV birth dose. As births in these locations become more common, targeted policies and education are warranted.

Precise spatiotemporal control of voltage-gated sodium channels by photocaged saxitoxin.

Here we report the pharmacologic blockade of voltage-gated sodium ion channels (NaVs) by a synthetic saxitoxin derivative affixed to a photocleavable protecting group. We demonstrate that a functionalized saxitoxin (STX-eac) enables exquisite spatiotemporal control of NaVs to interrupt action potentials in dissociated neurons and nerve fiber bundles. The photo-uncaged inhibitor (STX-ea) is a nanomolar potent, reversible binder of NaVs. We use STX-eac to reveal differential susceptibility of myelinated and unmyelinated axons in the corpus callosum to NaV-dependent alterations in action potential propagation, with unmyelinated axons preferentially showing reduced action potential fidelity under conditions of partial NaV block. These results validate STX-eac as a high precision tool for robust photocontrol of neuronal excitability and action potential generation.