Amyloid-beta/Fyn–Induced Synaptic, Network, and Cognitive Impairments Depend on Tau Levels in Multiple Mouse Models of Alzheimer’s Disease

Alzheimer\u27s disease (AD), the most common neurodegenerative disorder, is a growing public health problem and still lacks effective treatments. Recent evidence suggests that microtubule-associated protein tau may mediate amyloid-β peptide (Aβ) toxicity by modulating the tyrosine kinase Fyn.Weshowed previously that tau reduction prevents, and Fyn overexpression exacerbates, cognitive deficits in human amyloid precursor protein (hAPP) transgenic mice overexpressing Aβ. However, the mechanisms by which Aβ, tau, and Fyn cooperate in AD-related pathogenesis remain to be fully elucidated. Here we examined the synaptic and network effects of this pathogenic triad. Tau reduction prevented cognitive decline induced by synergistic effects of Aβ and Fyn. Tau reduction also prevented synaptic transmission and plasticity deficits in hAPP mice. Using electroencephalography to examine network effects, we found that tau reduction prevented spontaneous epileptiform activity in multiple lines of hAPP mice. Tau reduction also reduced the severity of spontaneous and chemically induced seizures in mice overexpressing both Aβ and Fyn. To better understand these protective effects, we recorded wholecell currents in acute hippocampal slices from hAPP mice with and without tau. hAPP mice with tau had increased spontaneous and evoked excitatory currents, reduced inhibitory currents, and NMDA receptor dysfunction. Tau reduction increased inhibitory currents and normalized excitation/inhibition balance and NMDA receptor-mediated currents in hAPP mice. Our results indicate that Aβ, tau, and Fyn jointly impair synaptic and network function and suggest that disrupting the copathogenic relationship between these factors could be of therapeutic benefit

A review of carbon monitoring in wet carbon systems using remote sensing

Carbon monitoring is critical for the reporting and verification of carbon stocks and change. Remote sensing is a tool increasingly used to estimate the spatial heterogeneity, extent and change of carbon stocks within and across various systems. We designate the use of the term wet carbon system to the interconnected wetlands, ocean, river and streams, lakes and ponds, and permafrost, which are carbon-dense and vital conduits for carbon throughout the terrestrial and aquatic sections of the carbon cycle. We reviewed wet carbon monitoring studies that utilize earth observation to improve our knowledge of data gaps, methods, and future research recommendations. To achieve this, we conducted a systematic review collecting 1622 references and screening them with a combination of text matching and a panel of three experts. The search found 496 references, with an additional 78 references added by experts. Our study found considerable variability of the utilization of remote sensing and global wet carbon monitoring progress across the nine systems analyzed. The review highlighted that remote sensing is routinely used to globally map carbon in mangroves and oceans, whereas seagrass, terrestrial wetlands, tidal marshes, rivers, and permafrost would benefit from more accurate and comprehensive global maps of extent. We identified three critical gaps and twelve recommendations to continue progressing wet carbon systems and increase cross system scientific inquiry

Pharmacological Analysis of Ionotropic Glutamate Receptor Function in Neuronal Circuits of the Zebrafish Olfactory Bulb

Although synaptic functions of ionotropic glutamate receptors in the olfactory bulb have been studied in vitro, their roles in pattern processing in the intact system remain controversial. We therefore examined the functions of ionotropic glutamate receptors during odor processing in the intact olfactory bulb of zebrafish using pharmacological manipulations. Odor responses of mitral cells and interneurons were recorded by electrophysiology and 2-photon Ca2+ imaging. The combined blockade of AMPA/kainate and NMDA receptors abolished odor-evoked excitation of mitral cells. The blockade of AMPA/kainate receptors alone, in contrast, increased the mean response of mitral cells and decreased the mean response of interneurons. The blockade of NMDA receptors caused little or no change in the mean responses of mitral cells and interneurons. However, antagonists of both receptor types had diverse effects on the magnitude and time course of individual mitral cell and interneuron responses and, thus, changed spatio-temporal activity patterns across neuronal populations. Oscillatory synchronization was abolished or reduced by AMPA/kainate and NMDA receptor antagonists, respectively. These results indicate that (1) interneuron responses depend mainly on AMPA/kainate receptor input during an odor response, (2) interactions among mitral cells and interneurons regulate the total olfactory bulb output activity, (3) AMPA/kainate receptors participate in the synchronization of odor-dependent neuronal ensembles, and (4) ionotropic glutamate receptor-containing synaptic circuits shape odor-specific patterns of olfactory bulb output activity. These mechanisms are likely to be important for the processing of odor-encoding activity patterns in the olfactory bulb

Assessment of the NASA carbon monitoring system wet carbon stakeholder community: data needs, gaps, and opportunities

Wet carbon (WC) ecosystems are a critical part of the carbon cycle, yet they are underrepresented in many policy and science communities due to the relative under-investment in stakeholder and boundary organizations. WC systems include the hydrosphere and carbon cycling systems that operate in wetlands, oceans, rivers, streams, lakes, ponds, and permafrost. In this article, we provide evidence from a desk review of WC stakeholders, that includes individuals, groups or organizations that are affected by climate change, and utilize carbon data. These stakeholders are involved in decision-making processes in WC ecosystems, and can be private companies, non-governmental organizations, government agencies ranging in scope from local to federal, parastatals, international organizations, and more. In this paper, we identify and describe the links and interests of WC stakeholders and analyze the gaps between scientific understanding and information needs. A continued focus on WC systems could lead to increased stakeholder engagement and methodological and scientific progress. Our study revealed that stakeholder interest in WC systems was not primarily determined by its role in the carbon cycle, but rather by its significance for local policy, economics, or ecology. To bridge the gap between stakeholders and available WC data, we need improved communication of data availability and uncertainty, capacity building, engagement between stakeholder groups, and data continuity. Enhanced stakeholder engagement across various systems will facilitate greater utilization of carbon monitoring data derived from remote sensing; thereby creating more informed stakeholders as well as more effective decision-making processes

Contribution of a calcium-activated non-specific conductance to NMDA receptor-mediated synaptic potentials in granule cells of the frog olfactory bulb

We studied granule cells (GCs) in the intact frog olfactory bulb (OB) by combining whole-cell recordings and functional two-photon Ca2+ imaging in an in vitro nose-brain preparation. GCs are local interneurones that shape OB output via distributed dendrodendritic inhibition of OB projection neurones, the mitral-tufted cells (MTCs). In contrast to MTCs, GCs exhibited a Ca2+-activated non-specific cation conductance (ICAN) that could be evoked through strong synaptic stimulation or suprathreshold current injection. Photolysis of the caged Ca2+ chelator o-nitrophenol-EGTA resulted in activation of an inward current with a reversal potential within the range -20 to +10 mV. ICAN in GCs was suppressed by the intracellular Ca2+ chelator BAPTA (0.5–5.0 mM), but not by EGTA (up to 5 mM). The current persisted in whole-cell recordings for up to 1.5 h post-breakthrough, was observed during perforated-patch recordings and was independent of ionotropic glutamate and GABAA receptor activity. In current-clamp mode, GC responses to synaptic stimulation consisted of an initial AMPA-mediated conductance followed by a late-phase APV-sensitive plateau (100–500 ms). BAPTA-mediated suppression of ICAN resulted in a selective reduction of the late component of the evoked synaptic potential, consistent with a positive feedback relationship between NMDA receptor (NMDAR) current and ICAN. ICAN requires Ca2+ influx either through voltage-gated Ca2+ channels or possibly NMDARs, both of which have a high threshold for activation in GCs, predicting a functional role for this current in the selective enhancement of strong synaptic inputs to GCs