Experience-dependent plasticity of the optomotor response in Drosophila melanogaster.

Experience in early life can affect the development of the nervous system. There is now evidence that experience-dependent plasticity exists in adult insects. To uncover the molecular basis of plasticity, an invertebrate model, such as Drosophila melanogaster, is a powerful tool, as many established genetic and molecular methods can be applied. To establish a model system in which behavioral plasticity can be examined, we investigated the optomotor response, a behavior common to most sight-reliant animals, in Drosophila and found that the response could be modified by the level of light during rearing. The angle turned by the head in response to a moving stimulus was used to quantify the response. Deprivation of light increased the response to low-contrast stimuli in wild-type Drosophila at 4 days after eclosion and this plastic change did not appear in rutabaga, a known mutant defective in short-term memory. In addition, the change was transient and was markedly decreased at 6 days after eclosion. Further, we found that Dark-flies, which have been kept in constant darkness for more than 50 years, showed a higher response to low-contrast stimuli even at 6 days after eclosion compared to wild type and this characteristic was not lost in Dark-flies placed in a normal light environment for 2 generations, suggesting that this high response has a hereditary nature. Thus, our model system can be used to examine how the environment affects behaviors.

Blockade of T-type calcium channels by 6-prenylnaringenin, a hop component, alleviates neuropathic and visceral pain in mice.

Since Cav3.2 T-type Ca2+ channels (T-channels) expressed in the primary afferents and CNS contribute to intractable pain, we explored T-channel-blocking components in distinct herbal extracts using a whole-cell patch-clamp technique in HEK293 cells stably expressing Cav3.2 or Cav3.1, and purified and identified sophoraflavanone G (SG) as an active compound from SOPHORAE RADIX (SR). Interestingly, hop-derived SG analogues, (2S)-6-prenylnaringenin (6-PNG) and (2S)-8-PNG, but not naringenin, also blocked T-channels; IC50 (µM) of SG, (2S)-6-PNG and (2S)-8-PNG was 0.68-0.75 for Cav3.2 and 0.99-1.41 for Cav3.1. (2S)-6-PNG and (2S)-8-PNG, but not SG, exhibited reversible inhibition. The racemic (2R/S)-6-PNG as well as (2S)-6-PNG potently blocked Cav3.2, but exhibited minor effect on high-voltage-activated Ca2+ channels and voltage-gated Na+ channels in differentiated NG108-15 cells. In mice, the mechanical allodynia following intraplantar (i.pl.) administration of an H2S donor was abolished by oral or i.p. SR extract and by i.pl. SG, (2S)-6-PNG or (2S)-8-PNG, but not naringenin. Intraperitoneal (2R/S)-6-PNG strongly suppressed visceral pain and spinal ERK phosphorylation following intracolonic administration of an H2S donor in mice. (2R/S)-6-PNG, administered i.pl. or i.p., suppressed the neuropathic allodynia induced by partial sciatic nerve ligation or oxaliplatin, an anti-cancer agent, in mice. (2R/S)-6-PNG had little or no effect on open-field behavior, motor performance or cardiovascular function in mice, and on the contractility of isolated rat aorta. (2R/S)-6-PNG, but not SG, was detectable in the brain after their i.p. administration in mice. Our data suggest that 6-PNG, a hop component, blocks T-channels, and alleviates neuropathic and visceral pain with little side effects.