Techniques for fast noninvasive control of neuronal excitability will be of major importance for analyzing and understanding neuronal networks and animal behavior. To develop these tools we demonstrated that two light-activated signaling proteins, vertebrate rat rhodopsin 4 (RO4) and the green algae channelrhodospin 2 (ChR2), could be used to control neuronal excitability and modulate synaptic transmission. Vertebrate rhodopsin couples to the Gi͞o, pertussis toxin-sensitive pathway to allow modulation of G protein-gated inward rectifying potassium channels and voltagegated Ca 2؉ channels. Light-mediated activation of RO4 in cultured hippocampal neurons reduces neuronal firing within ms by hyperpolarization of the somato-dendritic membrane and when activated at presynaptic sites modulates synaptic transmission and paired-pulse facilitation. In contrast, somato-dendritic activation of ChR2 depolarizes neurons sufficiently to induce immediate action potentials, which precisely follow the ChR2 activation up to light stimulation frequencies of 20 Hz. To demonstrate that these constructs are useful for regulating network behavior in intact organisms, embryonic chick spinal cords were electroporated with either construct, allowing the frequency of episodes of spontaneous bursting activity, known to be important for motor circuit formation, to be precisely controlled. Thus light-activated vertebrate RO4 and green algae ChR2 allow the antagonistic control of neuronal function within ms to s in a precise, reversible, and noninvasive manner in cultured neurons and intact vertebrate spinal cords.A major challenge in understanding the relationship between neural activity and development and between neuronal circuit activity and specific behaviors is to be able to control the activity of large populations of neurons or regions of individual nerve cells simultaneously. Recently, it was demonstrated that neuronal circuits can be manipulated by expressing mutated ion channels or G protein-coupled receptors (GPCRs). For example, the regional expression of a genetically modified K ϩ channel in Drosophila was able to reduce the excitability of targeted cells (i.e., muscle, neurons, photoreceptors) (1). Silencing of cortical neurons was achieved by binding of the peptide allostatin to its exogenously expressed receptor (2). Recently, Zemelman et al. (3) elegantly demonstrated that light activation of the protein complex, encoded by the Drosophila photoreceptor genes (i.e., arrestin-2, rhodopsin, and G protein ␣ subunit), could induce action potential firing of hippocampal neurons. Activation and deactivation of neuronal firing could also be achieved when ligand-gated ion channels, such as the capsaicin receptor, menthol receptor, purinergic receptors, or lightcontrollable K ϩ channel blockers, were used to control firing in hippocampal neurons (4, 5). However, the application of these techniques to control neuronal function especially in neural circuits and living animals is limited by their relatively slow time course, the complex...
Gain-of function mutations in some genes underlie neurodegenerative conditions whereas loss-of-function mutations have distinct phenotypes. Such appears to be the case with the protein ataxin 1 (ATXN1), which forms a transcriptional repressor complex with capicua (CIC). Gain-of-function of the complex leads to neurodegeneration, but ATXIN1-CIC is also essential for survival. We set out to understand the functions of ATXN1-CIC in the developing forebrain and found that losing the complex results in hyperactivity, impaired learning and memory, and abnormal maturation and maintenance of upper layer cortical neurons. We also found that CIC modulates social interactions in the hypothalamus and medial amygdala. Informed by these neurobehavioral features in mouse mutants, we identified five patients with de novo heterozygous truncating mutations in CIC that share similar clinical features, including intellectual disability, attention deficit/hyperactivity disorder (ADHD), and autism spectrum disorder. Our study demonstrates that loss of ATXN1-CIC complexes causes a spectrum of neurobehavioral phenotypes.
Abstract. Rangelands of China have for centuries provided forage for livestock but now their role in water, soil, and biodiversity conservation is being recognised by Governments and people. However, much of the rangelands has recently degraded and desertification is now a widespread problem. The cause of the degradation is over-grazing and over-cultivation. Climate change is exacerbating the problem. The Chinese Governments have begun to address these severe problems through policy adjustments and projects. In parallel, some research and development is taking place. There are major impediments to addressing the problem; the importance of rangelands to China and its people are generally underestimated, legislative protection is incomplete and often ineffective, little attention is paid to scientific knowledge for development of management of natural resources, there is insufficient technological support, and Governments are not able to invest sufficiently to effectively restore and develop rangeland natural resources. However, with this background we propose how the problems might be more effectively addressed in the future.
Seven flavonoids have been isolated from the aerial parts of Halostachys caspica C. A. Mey. (Chenopodiaceae) for the first time. By means of physicochemical and spectrometric analysis, they were identified as luteolin (1), chrysin (2), chrysin 7-O-β-D-glucopyranoside (3), quercetin (4), quercetin 3-O-β-D-glucopyranoside (5), isorhamentin-3-O-β-D-glucopyranoside (6), and isorhamentin-3-O-β-D-rutinoside (7). All flavonoids were evaluated to show a broad antimicrobial spectrum of activity on microorganisms including seven bacterial and one fungal species as well as pronounced antioxidant activity. Among them, the aglycones with relatively low polarity had stronger bioactivity than their glycosides. The results suggested that the isolated flavonoids could be used for future development of antimicrobial and antioxidant agents, and also provided additional data for supporting the use of H. caspica as forage.
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