Vertebrate retinas use fast neurotransmitters to signal moment-to-moment changes in the distribution of incident light. Retinas contain an additional set of neurotransmitters which operate on slower time scales to modulate signal flow and processing. My lab studies how action potentials and voltage-gated ion currents are modulated by such slow neurotransmitters, in retinal ganglion cells. The transmitter that interests us is dopamine, because light augments intraretinal dopamine release and because dopamine produces several effects that help retinas function, during daylight, as the most distal cells of the visual system. Our goal is to understand how dopamine alters ganglion cell excitability. We started this work by examining effects of dopamine on goldfish ganglion cells, because previous studies of this species identified the cells that release dopamine, some of the cells that respond to dopamine, conditions that release dopamine, and some consequences of depleting intraretinal dopamine. In ganglion cells of freshly isolated retinas, we found evidence that light-stimulated release of dopamine activates D1-type receptors and elevates cAMP (adenosine 3',5' cyclic monophosphate) levels. We then dissociated retinas and found that dopamine inhibit ganglion cell spike firing, that this inhibition entails cAMP-dependent protein kinase activation, and that this inhibition resembles certain effects of background light (Vaquero et al 2001). We are now working on several projects stemming from these results. First, we are using mammalian retinas to test whether dopamine generally serves as a 'light switch' at the level of ganglion cells. Secondly, we are analyzing a number of effects of dopamine and related ligands on isolated voltage-gated currents. Thirdly, we are identifying signaling cascade components that mediate ganglion cell responses to dopamine.

Courses Taught:

NPB 101 Systemic Physiology
NSC 261A Topics in Vision

Publications:

Oi H, Partida GJ, Lee SC, Ishida AT (2008). HCN4-like immunoreactivity in rat retinal ganglion cells. Visual Neuroscience 25: 95-102

Lee SC, Ishida AT (2007). I(h) without K(ir) in adult rat retinal ganglion cells. Journal of Neurophysiology 97: 3790-3799

Partida GJ, SC Lee, L Haft-Candell, GS Nichols, AT Ishida (2004). DARPP-32-like immunoreactivity in AII amacrine cells of rat retina. Journal of Comparative Neurology 480: 251-263

Hayashida Y, AT Ishida (2004). Dopamine receptor activation can reduce voltage-gated Na+ current by modulating both entry into and recovery from inactivation. Journal of Neurophysiology 92: 3134-3141

Hayashida Y, GJ Partida, AT Ishida (2004). Dissociation of retinal ganglion cells without enzymes. Journal of Neuroscience Methods 137: 25-35

Ishida AT (2004). Retinal ganglion cell excitability. In: LM Chalupa and JS Werner (Eds.) The Visual Neurosciences. Cambridge, MA. MIT Press. pp 422-450

Lee SC, Y Hayashida, AT Ishida (2003). Availability of low-threshold Ca2+ current in retinal ganglion cells. Journal of Neurophysiology 90: 3888-3901

Vaquero CF, A Pignatelli, GJ Partida, AT Ishida (2001). A dopamine- and protein kinase A-dependent mechanism for network adaptation in retinal ganglion cells. Journal of Neuroscience 21:8624-8635

Tabata T, AT Ishida (1999). A zinc-dependent Cl- current in neuronal somata. Journal of Neuroscience 19:5195-5204