Volume transmission of dopamine may modulate light-adaptive plasticity of horizontal cell dendrites in the recovery phase following dopamine depletion in goldfish retina.

We investigated the recovery of light-adaptive spinule formation following dopamine depletion with intraocular injection of 6-hydroxydopamine (6-OHDA) and subsequent neogeneration of dopamine interplexiform cells (DA-IPC) at the marginal zone. DA-IPCs were gone by 2 weeks postinjection and appeared at the marginal zone by 6 weeks postinjection, at which time DA-IPC neurites grew toward the central retina, reaching within 0.5 mm of the central retina by 1 year. Retinas from day time, light-adapted fish at 2 weeks, 4 weeks, 3 months, and 1 year postinjection with 6-OHDA were processed for pre-embedding tyrosine hydroxylase immunoreactivity (TOH-IR) and compared to sham-injected and control retinas at the electron-microscopical (EM) level. Only 6-OHDA fish that tilted markedly toward the injected eye were used for these experiments. The tilt mimics the dorsal light reaction, indicating a 2-2.5 log unit increase in the photopic sensitivity of the 6-OHDA eye. Spinule formation was reduced by about 60% in the 2- and 4-week 6-OHDA retinas, but returned to control levels throughout the entire retina of 3-month and 1 year 6-OHDA retinas even though the central region of these retinas contained no detectable TOH-IR. Intraocular injection with 10 microM SCH 23390 (a D1 antagonist) reduced light-adaptive spinule formation by 50% both in control eyes as well as those eyes that were 3 months post 6-OHDA injected. The full return of spinule formation with only partial reinnervation of the retina with DA-IPC processes and their subsequent inhibition by SCH 23390 indicates that dopamine diffused large distances within the retina to regulate this synaptic plasticity (i.e. displayed volume transmission). Also, since all 6-OHDA injected fish displayed an increased photopic sensitivity in the injected eye when sacrificed, we suggest that horizontal cell spinules are not required for photopic luminosity coding in the outer retina.