Microglia have crucial roles in sculpting synapses and maintaining neural circuits during development. To test the hypothesis that microglia continue to regulate neural circuit connectivity in adult brain, we have investigated the effects of chronic microglial depletion, via CSF1R inhibition, on synaptic connectivity in the visual cortex in adult mice of both sexes. We find that the absence of microglia dramatically increases both excitatory and inhibitory synaptic connections to excitatory cortical neurons assessed with functional circuit mapping experiments in acutely prepared adult brain slices. Microglia depletion leads to increased densities and intensities of perineuronal nets. Furthermore, in vivo calcium imaging across large populations of visual cortical neurons reveals enhanced neural activities of both excitatory neurons and parvalbumin-expressing interneurons in the visual cortex following microglia depletion. These changes recover following adult microglia repopulation. In summary, our new results demonstrate a prominent role of microglia in sculpting neuronal circuit connectivity and regulating subsequent functional activity in adult cortex.

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Hydride transfer is a critical elementary reaction step that spans biological catalysis, organic synthesis, and energy conversion. Conventionally, hydride transfer reactions are carried out using (bio)molecular hydride reagents under homogeneous conditions. Herein, we report a conceptually distinct heterogeneous hydride transfer reaction via the net electrocatalytic hydrogen reduction reaction (HRR) which reduces H 2 to hydrides. The reaction proceeds by H 2 dissociative adsorption on a metal electrode to form surface M−H species, which are then negatively polarized to drive hydride transfer to molecular hydride acceptors with up to 95% Faradaic e ciency. We nd that the hydride transfer reactivity of surface M−H species is highly tunable and its thermochemistry depends on the applied potential in a Nernstian fashion. Thus, depending on the electrode potential, we observe that the thermodynamic hydricity of Pt−H on the same Pt electrode can continuously span a range of >40 kcal mol −1 . This work highlights the critical role of electrical polarization on heterogeneous hydride transfer reactivity and establishes a sustainable strategy for accessing reactive hydrides directly from H 2 .

Heterogeneous electrocatalysis involves elementary chemical and charge transfer reaction steps, with the kinetics of each step contributing to the overpotential requirement at a given reaction rate. Typical experiments report on the aggregate rate-overpotential profile with no information about the relative contributions from charge transfer and chemical steps. For the hydrogen evolution reaction (HER), the applied overpotential can be partitioned into a charge transfer overpotential, the overpotential necessary to drive proton-coupled electron transfer (PCET) to and from the surface, and a chemical overpotential, corresponding to a change in surface H activity. Reaction conditions can affect either or both the charge transfer and chemical components. Herein, we employ a Pd membrane double cell to spatially separate the charge transfer and chemical reactions steps of HER catalysis, enabling quantification of the chemical and charge transfer overpotential. We further analyze how each depend on pH, and the introduction of HER poisons and promoters. We find that for a given rate of H2 release, the chemical overpotential is constant across diverse reaction environments whereas the charge transfer overpotential is strongly sensitive to reaction conditions. These findings suggest that reaction condition dependent-HER efficiencies are driven predominantly by changes to the kinetics of charge transfer rather than the chemical reactivity of surface H.

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