Behavioral destabilization induced by the selective serotonin reuptake inhibitor fluoxetine

<p>Abstract</p> <p>Background</p> <p>Selective serotonin reuptake inhibitors (SSRIs) are widely used to treat mood and anxiety disorders. However, neuronal bases for both beneficial and adverse effects of SSRIs remain poorly understood. We have recently shown that the SSRI fluoxetine can reverse the state of maturation of hippocampal granule cells in adult mice. The granule cell "dematuration" is induced in a large population of granule cells, and greatly changes functional and physiological properties of these cells. Here we show that this unique form of neuronal plasticity is correlated with a distinct change in behavior of mice.</p> <p>Results</p> <p>We chronically treated adult male mice with fluoxetine, and examined its effect on several forms of behavior of mice. During fluoxetine treatments, mice showed a marked increase in day-to-day fluctuations of home cage activity levels that was characterized by occasional switching between hypoactivity and hyperactivity within a few days. This destabilized cage activity was accompanied by increased anxiety-related behaviors and could be observed up to 4 weeks after withdrawal from fluoxetine. As reported previously, the granule cell dematuration by fluoxetine includes a reduction of synaptic facilitation at the granule cell output, mossy fiber, synapse to the juvenile level. Mossy fiber synaptic facilitation examined electrophysiologically in acute hippocampal slices also remained suppressed after fluoxetine withdrawal and significantly correlated with the fluctuation of cage activity levels in individual mice. Furthermore, in mice lacking the 5-HT₄receptor, in which the granule cell dematuration has been shown to be attenuated, fluoxetine had no significant effect on the fluctuation of cage activity levels.</p> <p>Conclusions</p> <p>Our results demonstrate that the SSRI fluoxetine can induce marked day-to-day changes in activity levels of mice in the familiar environment, and that the dematuration of the hippocampal granule cells is closely associated with the expression of this destabilized behavior. Based on these results, we propose that the granule cell dematuration can be a potential cellular basis underlying switching-like changes in the behavioral state associated with SSRI treatments.</p

Development of a reinforced Ti-eviction plasmid useful for construction of Ti plasmid-free Agrobacterium strains

For curing stable Ti plasmids from Agrobacterium strains, we developed a new Ti-eviction plasmid. The plasmid contains two antitoxin genes, which originated from two toxin-antitoxin systems in Ti plasmids. The plasmid facilitated production of Ti-less cells in seven tested strains, and was removed easily by simple counter-selection from the cells.This work was supported in part by the Japanese Ministry of Education, Science, Sports, and Culture, Grant-in-Aid for Scientific Research (grant 20570221)

Ecological and Histological Notes on the Luminous Springtail, <em>Lobella</em> sp. (Collembola: Neanuridae), Discovered in Tokyo, Japan

Some species of springtail (Collembola) are luminous, but it is not known whether light emitted by springtail is due to self-luminescence, feeding on luminous fungi, or accidental infection by luminous bacteria. To address this question, we characterized the luminescence of a luminous springtail, Lobella sp. (family Neanuridae) discovered in Tokyo, Japan. The emitted light was yellowish-green (540 nm) and was found to originate from tubercles on the thorax (segments II and III) and abdomen (segments I–VI) using a low-light imaging system. The luminescence persisted for several seconds but showed occasional oscillations in a laboratory environment. We also observed fat bodies containing eosin-positive granules under the integument of the tubercles in the tergum by hematoxylin and eosin (HE) staining that were not present in a nonluminous springtail (Vitronura sp.). The fat bodies in Lobella sp. are presumably photocytes analogous to the firefly lantern, and the eosin-positive granules are the likely source of bioluminescence, which implies that springtails are self-luminescent