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General anesthesia is characterized by reversible loss of consciousness accompanied by transient amnesia. Yet, long-term memory impairment is an undesirable side effect. How different types of general anesthetics (GAs) affect the hippocampus, a brain region central to memory formation and consolidation, is poorly understood. Using extracellular recordings, chronic 2-photon imaging, and behavioral analysis, we monitor the effects of isoflurane (Iso), medetomidine/midazolam/fentanyl (MMF), and ketamine/xylazine (Keta/Xyl) on network activity and structural spine dynamics in the hippocampal CA1 area of adult mice. GAs robustly reduced spiking activity, decorrelated cellular ensembles, albeit with distinct activity signatures, and altered spine dynamics. CA1 network activity under all 3 anesthetics was different to natural sleep. Iso anesthesia most closely resembled unperturbed activity during wakefulness and sleep, and network alterations recovered more readily than with Keta/Xyl and MMF. Correspondingly, memory consolidation was impaired after exposure to Keta/Xyl and MMF, but not Iso. Thus, different anesthetics distinctly alter hippocampal network dynamics, synaptic connectivity, and memory consolidation, with implications for GA strategy appraisal in animal research and clinical settings.

The acute effects of anesthesia and their underlying mechanisms are still not fully understood. Thus, comprehensive analysis and efficient generalization require their description in various brain regions. Here we describe a large-scale, annotated collection of 2-photon calcium imaging data and multi-electrode, extracellular electrophysiological recordings in CA1 of the murine hippocampus under three distinct anesthetics (Isoflurane, Ketamine/Xylazine and Medetomidine/Midazolam/Fentanyl), during natural sleep, and wakefulness. We cover several aspects of data quality standardization and provide a set of tools for autonomous validation, along with analysis workflows for reuse and data exploration. The datasets described here capture various aspects of neural activity in hundreds of pyramidal cells at single cell resolution. In addition to relevance for basic biological research, the dataset may find utility in computational neuroscience as a benchmark for models of anesthesia and sleep.Measurement(s)brain activity measurement • pupil dilationTechnology Type(s)two-photon calcium imaging • local field potential recording • videographyFactor Type(s)calcium imaging data • local field potentialsSample Characteristic - OrganismMus musculus

Solar neutrinos have played a central role in the discovery of the neutrino oscillation mechanism. They still are proving to be a unique tool to help investigate the fusion reactions that power stars and further probe basic neutrino properties. The Borexino neutrino observatory has been operationally acquiring data at Laboratori Nazionali del Gran Sasso in Italy since 2007. Its main goal is the real-time study of low energy neutrinos (solar or originated elsewhere, such as geo-neutrinos). The latest analysis of experimental data, taken during the so-called Borexino Phase-II (2011-present), will be showcased in this talk—yielding new high-precision, simultaneous wide band flux measurements of the four main solar neutrino components belonging to the “pp” fusion chain (pp, pep, 7 Be, 8 B), as well as upper limits on the remaining two solar neutrino fluxes (CNO and hep).

Fiber photometry is a technique of growing popularity in neuroscientific research. It is widely used to infer brain activity by recording calcium dynamics in genetically defined populations of neurons. Aside from the wide variety of calcium indicators, other genetically encoded biosensors have recently been engineered to measure membrane potential, neurotransmitter release, pH, or various cellular metabolites, such as ATP or cAMP. Due to the spectral characteristics of these molecular tools, different assemblies of optical hardware are usually needed to reveal the full potential of different biosensors. In addition, the combination of multiple biosensors in one experiment often requires the investment in more complex equipment, which limits the flexibility of the experimental design. Such constraints often hamper a straightforward implementation of new molecular tools, evaluation of their performance in vivo, and design of new experimental paradigms - especially if the financial budget is a limiting factor. Here, we propose a novel approach for fiber photometry recordings, based on a multimode optical fused-fiber coupler (FFC) for both light delivery and collection. Recordings can readily be combined with optogenetic manipulations in a single device without the requirement for dichroic beam-splitters. In combination with a multi-color light source and appropriate emission filters, our approach offers remarkable flexibility in experimental design and facilitates the implication of new molecular tools in vivo at minimal cost. The ease of assembly, operation, characterization, and customization of this platform holds the potential to foster the development of experimental strategies for multicolor fused fiber photometry (FFP) combined with optogenetics far beyond its current state. Competing Interest Statement The authors have a patent application pending for the use of fused fiber optics for bidirectional communication with electrically excitable cells (50/25/25 % by AF/AD/JSW). A European patent application has been filed under the Nr. 22162303.6

Expression of the immediate early gene cFos modifies the epigenetic landscape of activated neurons with downstream effects on synaptic plasticity. The production of cFos is inhibited by a long-lived isoform of another Fos family gene, ΔFosB. It has been speculated that this negative feedback mechanism may be critical for protecting episodic memories from being overwritten by new information. Here, we investigate the influence of ΔFosB inhibition on cFos expression and memory. Hippocampal neurons in slice culture produce more cFos on the first day of stimulation compared to identical stimulation on the following day. This downregulation affects all hippocampal subfields and requires histone deacetylation. Overexpression of ΔFosB in individual pyramidal neurons effectively suppresses cFos, indicating that accumulation of ΔFosB is the causal mechanism. Water maze training of mice over several days leads to accumulation of ΔFosB in granule cells of the dentate gyrus, but not in CA3 and CA1. Because the dentate gyrus is thought to support pattern separation and cognitive flexibility, we hypothesized that inhibiting the expression of ΔFosB would affect reversal learning, i.e., the ability to successively learn new platform locations in the water maze. The results indicate that pharmacological HDAC inhibition, which prevents cFos repression, impairs reversal learning, while learning and memory of the initial platform location remain unaffected. Our study supports the hypothesis that epigenetic mechanisms tightly regulate cFos expression in individual granule cells to orchestrate the formation of time-stamped memories.Competing Interest StatementThe authors have declared no competing interest.

ABSTRACT General anesthesia is characterized by reversible loss of consciousness accompanied by transient amnesia. Yet, long-term memory impairment is an undesirable side-effect. How different types of general anesthetics (GAs) affect the hippocampus, a brain region central to memory formation and consolidation, is poorly understood. Using extracellular recordings, chronic 2-photon imaging and behavioral analysis, we monitor the effects of isoflurane (Iso), medetomidine/midazolam/fentanyl (MMF), and ketamine/xylazine (Keta/Xyl) on network activity and structural spine dynamics in the hippocampal CA1 area of adult mice. GAs robustly reduced spiking activity, decorrelated cellular ensembles, albeit with distinct activity signatures, and altered spine dynamics. CA1 network activity under all three anesthetics was different to natural sleep. Iso anesthesia most closely resembled unperturbed activity during wakefulness and sleep, and network alterations recovered more readily than with Keta/Xyl and MMF. Correspondingly, memory consolidation was impaired after exposure to Keta/Xyl and MMF, but not Iso. Thus, different anesthetics distinctly alter hippocampal network dynamics, synaptic connectivity, and memory consolidation, with implications for GA strategy appraisal in animal research and clinical settings. Competing Interest Statement The authors have declared no competing interest. Footnotes * https://gin.g-node.org/SW_lab/Anesthesia_CA1 * https://github.com/mchini/Yang_Chini_et_al