APB (DL-2-amino-4-phosphonobutyric acid) has been found to affect the retinal processing of many vertebrate species as evidenced by the suppression of the b-wave component of the electroretinogram (ERG). The present study examined the effects of APB on the cone contributions to the ERG response of adult zebrafish (Danio rerio). ERG responses were obtained from light-adapted adult zebrafish following intravitreal injection of either saline alone or saline with various concentrations of APB ranging from 10 microm to 500 microM. Visual stimuli were 200-ms flashes of various wavelengths and irradiances. Spectral sensitivity functions were calculated from the irradiance versus response amplitude functions of the a-, b-, and d-wave components of the ERG response. Saline had no effects on the ERG response. However, APB had differential effects on the sensitivity of the b- and d-wave components. The effects of APB on the b-wave component were most apparent in the ultraviolet and short-wavelength portions (320-440 nm) of the spectral sensitivity function, although the b-wave was not completely eliminated at these wavelengths. APB-treated subjects were found to possess the same cone mechanisms (L-M and M-S) in the middle- and long-wavelength areas of the spectrum as saline injected subjects, although absolute sensitivity was lower for the APB-injected subjects. Spectral sensitivity based on the d-wave response was affected by APB but only in the short-wavelength region. All results appear to be independent of the APB dose. These results support the notion that glutamate receptors play a specific role in zebrafish visual processing. In addition, the effects of APB support recent anatomical evidence that the zebrafish retina may possess different types of glutamate receptors.

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1These authors contributed equally to this study.Abbreviations used:BrdU, bromodeoxyuridine; cDNA, complementary DNA; EGF, epidermal growth factor; FGF, fibroblast growth factor; FGFR, FGF receptor; NPY, neuropeptide YNSC, neural stem cell; NSPC, neural stem progenitor cell; SGZ, subgranular zone. AbstractWe have shown that neuropeptide Y (NPY), a peptide neurotransmitter released by hippocampal interneurons, is proliferative for hippocampal neural stem progenitor cells (NSPCs) via the Y1 receptor. Fibroblast growth factor (FGF) 2, released predominantly by astrocytes, is also a powerful mitogen for postnatal and adult NSPCs, via the FGFR1 receptor. Knockout studies show that NPY and FGF2 are individually necessary, but not sufficient, for seizure-induced neurogenesis, suggesting a possible interaction. Here, we examined for interactions between NPY and FGF2 on NSPCs from the postnatal hippocampus and report that the combination of NPY and FGF2 significantly shortens the cell cycle time of nestin positive NSPCs, more than either factor alone. This augmentation of proliferation rate is NPY Y1 receptor mediated, and Y1 receptor activation increases both FGFR1 mRNA and protein in NSPC cultures. NSPCs immunostain for both Y1 and FGFR1 receptors and the interaction is specific for dentate NSPCs. This is the first report of a proliferative factor that augments the proliferative effect of FGF2 and is the first evidence of a positive proliferative interaction between a glial growth factor and a neuronal transmitter, identifying a novel neural activity driven mechanism for modulating the proliferation of hippocampal NSPCs.

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