Severe behavioural deficits in psychiatric diseases such as autism and schizophrenia have been hypothesized to arise from elevations in the cellular balance of excitation and inhibition (E/I balance) within neural microcircuitry. This hypothesis could unify diverse streams of pathophysiological and genetic evidence, but has not been susceptible to direct testing. Here we design and use several novel optogenetic tools to causally investigate the cellular E/I balance hypothesis in freely moving mammals, and explore the associated circuit physiology. Elevation, but not reduction, of cellular E/I balance within the mouse medial prefrontal cortex was found to elicit a profound impairment in cellular information processing, associated with specific behavioural impairments and increased high-frequency power in the 30–80 Hz range, which have both been observed in clinical conditions in humans. Consistent with the E/I balance hypothesis, compensatory elevation of inhibitory cell excitability partially rescued social deficits caused by E/I balance elevation. These results provide support for the elevated cellular E/I balance hypothesis of severe neuropsychiatric disease-related symptoms.

Channelrhodopsin-2 (ChR2) is a microbial type rhodopsin and a light-gated cation channel that controls phototaxis in Chlamydomonas. We expressed ChR2 in COS-cells, purified it, and subsequently investigated this unusual photoreceptor by flash photolysis and UV-visible and Fourier transform infrared difference spectroscopy. Several transient photoproducts of the wild type ChR2 were identified, and their kinetics and molecular properties were compared with those of the ChR2 mutant E90Q. Based on the spectroscopic data we developed a model of the photocycle comprising six distinguishable intermediates. This photocycle shows similarities to the photocycle of the ChR2-related Channelrhodopsin of Volvox but also displays significant differences. We show that molecular changes include retinal isomerization, changes in hydrogen bonding of carboxylic acids, and large alterations of the protein backbone structure. These alterations are stronger than those observed in the photocycle of other microbial rhodopsins like bacteriorhodopsin and are related to those occurring in animal rhodopsins. UV-visible and Fourier transform infrared difference spectroscopy revealed two late intermediates with different time constants of ‫؍‬ 6 and 40 s that exist during the recovery of the dark state. The carboxylic side chain of Glu 90 is involved in the slow transition. The molecular changes during the ChR2 photocycle are discussed with respect to other members of the rhodopsin family. Channelrhodopsins (ChRs)3 are light-gated cation channels (1, 2) that share homology with other microbial rhodopsins such as bacteriorhodopsin (BR), halorhodopsin (HR), and sensory rhodopsin (SR). In nature they serve as sensory photoreceptors for phobic responses and phototaxis in green algae (3-5). The light-induced ion conductance leads to depolarization of the cell membrane within milliseconds. Because of this property, in recent years ChRs have been widely used in the neuroscience field as a tool for depolarization of selected cell types or cell ensembles (6, 7). Furthermore, channelrhodopsins were used to control neuronal activity in Caenorhabditis elegans, Drosophila, zebrafish, chicken embryos, and mice (8 -13).As is typical for rhodopsins, light absorption induces isomerization of the ChR-chromophore with subsequent conformational changes in the protein (photocycle). Based on UV-visible spectroscopic and electrophysiological measurements, several schemes for this photocycle have been presented. A recent model for recombinant Volvox channelrhodopsin (VChR), purified from green monkey COS cells, comprises the two dark states D470 and D480, characterized by a fine structured UVvisible absorption spectrum with maxima at 470 and 480 nm, respectively (14). These two states, which exist in a pH-dependent equilibrium, are both converted by light via retinal isomerization and transient Schiff base deprotonation to the conducting state P510 or, under acidic conditions, to P530. These intermediates thermally relax back to the dark state equilibrium in a biphas...

Diatoms are important primary producers not only in the oceans but also in the freshwater environment. The efficiency of biomass formation strongly depends on the metabolic regulation of carbon and nutrient assimilation. Recent studies have given evidence that many metabolic regulations are quite different from green algae and higher plants. The major known differences concern the following processes: (1) pigment biosynthesis, (2) lightharvesting organisation, (3) mechanism of photoprotection, (4) regulation of photosynthetic electron flow, (5) regulation of the enzyme activity in the Calvin-Benson cycle, (6) photorespiration, (7) carbon aquisition and CO 2-concentrating mechanisms, (8) synthesis and breakdown of storage products under starvation, (8) nutrient uptake (9) adaptation to extreme environments. This review summarises these differences phenomenologically and presents the actual knowledge of the underlying mechanisms. The availability of whole genome sequence data is an important basis to learn in more detail how photosynthesis in these tremendously successful primary producers is regulated.

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Channelrhodopsins (ChR) are light-gated ion channels of green algae that are widely used to probe the function of neuronal cells with light. Most ChRs show a substantial reduction in photocurrents during illumination, a process named "light adaptation". The main objective of this spectroscopic study was to elucidate the molecular processes associated with light-dark adaptation. Here we show by liquid and solid-state nuclear magnetic resonance spectroscopy that the retinal chromophore of fully dark-adapted ChR is exclusively in an all-trans configuration. Resonance Raman (RR) spectroscopy, however, revealed that already low light intensities establish a photostationary equilibrium between all-trans,15-anti and 13-cis,15-syn configurations at a ratio of 3:1. The underlying photoreactions involve simultaneous isomerization of the C(13)═C(14) and C(15)═N bonds. Both isomers of this DAapp state may run through photoinduced reaction cycles initiated by photoisomerization of only the C(13)═C(14) bond. RR spectroscopic experiments further demonstrated that photoinduced conversion of the apparent dark-adapted (DAapp) state to the photocycle intermediates P500 and P390 is distinctly more efficient for the all-trans isomer than for the 13-cis isomer, possibly because of different chromophore-water interactions. Our data demonstrating two complementary photocycles of the DAapp isomers are fully consistent with the existence of two conducting states that vary in quantitative relation during light-dark adaptation, as suggested previously by electrical measurements.