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Hyperactivity is observed in early Alzheimers disease (AD) in multiple brain regions, including the visual cortex. We recently found that the postsynaptic structures favor visual cortex hyperactivity, which disrupts functional connectivity and leads to visual recognition memory deficits in a mouse AD model. It is unclear whether presynaptic structures also favor hyperactivity and whether hyperactivity depends on the target or source of presynaptic terminals. In addition, it is not well understood whether the functional connectivity of brain regions under nonpathological conditions predicts their hyperactivity in amyloid pathology. We used c-Fos immunolabeling under resting state conditions to map brain-wide neural activity and performed network analysis. We also quantified excitatory and inhibitory presynaptic terminals in hyperactive and non-hyperactive brain regions.We found that hyperactivity in the visual network originates in the cortex, and brain regions highly connected to the primary visual cortex in nonpathological conditions tend to be hyperactive in amyloid pathology. Immunolabeling presynaptic terminals from subcortical and cortical neurons show that the source rather than the target brain regions determine the vulnerability of synapses. Furthermore, we observed a reduction in presynaptic structures selectively in the hyperactive region, indicating presynaptic changes are unfavorable to hyperactivity. Brain regions with higher functional connectivity under nonpathological conditions are vulnerable to hyperactivity in amyloid pathology. Furthermore, presynapse loss may serve as an adaptation to maintain neuronal activity homeostasis.

Abstract. A fundamental goal of satellite weather and climate observations is profiling the atmosphere with in situ-like precision and resolution with absolute accuracy and unbiased, all-weather, global coverage. While GPS radio occultation (RO) has perhaps come closest in terms of profiling the gas state from orbit, it does not provide sufficient information to simultaneously profile water vapor and temperature. We have been developing the Active Temperature, Ozone and Moisture Microwave Spectrometer (ATOMMS) RO system that probes the 22 and 183 GHz water vapor absorption lines to simultaneously profile temperature and water vapor from the lower troposphere to the mesopause. Using an ATOMMS instrument prototype between two mountaintops, we have demonstrated its ability to penetrate through water vapor, clouds and rain up to optical depths of 17 (7 orders of magnitude reduction in signal power) and still isolate the vapor absorption line spectrum to retrieve water vapor with a random uncertainty of less than 1 %. This demonstration represents a key step toward an orbiting ATOMMS system for weather, climate and constraining processes. ATOMMS water vapor retrievals from orbit will not be biased by climatological or first-guess constraints and will be capable of capturing nearly the full range of variability through the atmosphere and around the globe, in both clear and cloudy conditions, and will therefore greatly improve our understanding and analysis of water vapor. This information can be used to improve weather and climate models through constraints on and refinement of processes affecting and affected by water vapor.