Optogenetic silencing allows to reveal the necessity of selected neuronal populations for various neurophysiological functions. These range from synaptic transmission and coordinated neuronal network activity to control of specific behaviors. An ideal single-component optogenetic silencing tool should be switchable between active and inactive states with precise timing while preserving its activity in the absence of light until switched to an inactive state. Although bistable anion-conducting channelrhodopsins (ACRs) were previously engineered to reach this goal, their conducting state lifetime was limited to only a few minutes and some ACRs were not fully switchable. Here we report Aion, a bistable ACR displaying a long-lasting open state with a spontaneous closing time constant close to 15 min. Moreover, Aion can be switched between the open and closed state with millisecond precision using blue and orange light, respectively. The long conducting state enables overnight silencing of neurons with minimal light exposure. We further generated trafficking-optimized versions of Aion, which show enhanced membrane localization and allow precisely timed, long-lasting all-optical control of nociceptive responses in larvae of Drosophila melanogaster. Thus, Aion is an optogenetic silencing tool for inhibition of neuronal activity over many hours which can be switched between an active and inactive state with millisecond precision.

In a study designed to see the effect of various chemicals on root-tip mitosis of Pterotheca falconeri we were surprised to find reductional divisions like those at meiosis occurring in an appreciable frequency on treatment with caffeine. This led us to make a detailed systematic study not only of caffeine but also of other purine and pyrimidine derivatives, and the nucleic acids DNA and RNA. In the present paper the effect of caffeine, xanthosine and xanthine is presented. It must, however, be stated at the outset that besides "meiotic reductions" and reductional groupings, other cytological aberrations have also been noticed which will be con sidered separately in a subsequent publication.Before describing the results it is pertinent to clarify certain terminologies to avoid confusion. These are i) reductional groupings-not an uncommon phenom enon which occurs when the spindle is disrupted due to excitations or viscosity changes in the cytoplasm. Here the chromosomes separate merely quantitatively into two equal or unequal groups with an uneven distribution of the homologues. This is the effect of colchicine and sulfanilamide (see Mehra 1946Mehra , 1949) and other spindle inhibiting substances. In contrast, ii) "meiotic reductions" is a very precise qualitative phenomenon where the homologous chromosomes separate into two equal groups very much as they do during normal meiosis. Even the resultant haploid nuclei may undergo an equational division as at meiosis.A significant contribution in this field was made by Huskins (1948) who studied the effect of sodium deoxyribose nucleate on the root-tips of Allium cepa. Un fortunately this was not an ideal material in as much as the individual chromosomes of the haploid set, n=8, could not be easily identified. However, Huskins pro duced evidence, by no means conclusive, but certainly suggestive, of what he designated as "somatic meiosis" on the basis of 8: 8 separation of chromosomes in about 2% of the dividing cells. He also noticed an apparent segregation of chromosomes into two groups at late prophase as a result of the action of this chemical. Kodani (1948) from the same laboratory dealt with the effect of sodium ribose nucleate on the root-tips of Allium cepa and found C-metaphases, extreme condensation of chromosomes, aberrant anaphases with sticky equatorial bridges, and in addition reductional groupings into 0:16, 3:13 and 5:11 chromosomes. Allen et al. (1950) made a comparative study of the effects of colchicine and 1 Present address:

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