Activity sharpens the regenerating retinotectal projection in goldfish: Sensitive period for strobe illumination and lack of effect on synaptogenesis and on ganglion cell receptive field properties

Abstract

The regenerating optic nerve of goldfish first reestablishes a rough retinotopic map on the contralateral tectum and then sharpens it. Disruption of visual activity, either by blocking activity with intraocular tetrodotoxin (TTX; Schmidt and Edwards, 1983) or by synchronizing activity with strobe illumination (Schmidt and Eisele, 1985), disrupts the sharpening process: the map is correctly oriented but the multiunit receptive fields at each point average 25-40 degrees in diameter. In order to test whether strobe and TTX interfere with the same mechanism, we have tested whether their sensitive periods are the same, and whether strobe, like TTX treatment, does not affect either ganglion cell receptive field properties or synaptogenesis. In parallel studies, we exposed fish to 2 weeks of either strobe illumination or intraocular TTX beginning at various times after crush and determined via electrophysiological recordings that the periods of sensitivity were nearly identical. There was no effect of either treatment during the first 2 weeks (before the fibers arrive at the tectum), maximal disruption of sharpening between 14 and 50 days (the period of rapid synaptogenesis), decreasing disruption between 50 and 125 days, and no effect beyond that point or in the normal projection. In addition, long strobe exposures of up to 142 days produced no greater disruptions than shorter 2-3-week exposures, indicating no cumulative effect. The reestablishment of synaptic transmission in tectum, assayed by recording field potentials elicited by optic nerve shock, was not affected by stroboscopic illumination. Finally, individual ganglion cells, recorded intraretinally following long-term strobe exposure, had receptive fields that were normal both in size and in their characteristic responses to light-on, to light-off, or to both on and off. These findings support the hypothesis that strobe-like TTX prevents retinotopic refinement by preventing the correction of errors initially made by the ingrowing optic axons (Schmidt et al., 1988).

Myosin light chain kinase: expression in neurons and upregulation during axon regeneration

“…Regenerating optic axons initially arrive at the optic tectum as early as 14 days after optic nerve crush . Because the peak of GFMLCKl mRNA expression occurred before this time, we concluded that this upregulation more closely coincided with the pe- nod of active axonal outgrowth (Schmidt et al, 1983 ) rather than with that of synaptogenesis or retinotopic map sharpening (Eisele and Schmidt, 1988). This correlation is consistent with GFMLCKl as the source of the MLCK activity that was previously shown by pharmacological inhibitors to be essential for growth cone motility (Jian et al, 1994).…”

“…In fish of this size kept at 20°C, the first fibers reach the rostral edge of the tectum at around 14 days and synapse formation is first detectable electrophysiologicall y in extreme rostral tectum around 20 days (Schmidt et al, 1983). Retinotopic map sharpening also occurs later, ensuing after synaptogenesis (Eisele and Schmidt, 1988), and GFMLCK 1 expression greatly subsides before either is underway. Thus, there is a good correlation of high MLCK expression with the period of axon elongation.…”

“…The time courses of axonal outgrowth, synaptogenesis, and map refinement are well established (Schmidt et al, 1983Eisele and Schmidt, 1988). Therefore, studying a particular gene's expression in ganglion cells during the course of optic nerve regeneration should provide clues as to whether, and in which process( es), the gene product may participate.…”

Activity‐driven sharpening of the regenerating retinotectal projection: Effects of blocking or synchronizing activity on the morphology of individual regenerating arbors

“…Normal arbors were very planar and stratified, with the fine caliber the most superficial, the coarse next deeper, and the medium the deepest. Mature, regenerated arbors (examined at 6 months postcrush) reestablished these same three classes of arbors and calibers of axons (Schmidt et al, 1988). The sizes were approximately the same, and they had roughly the same number and order of branch endings and terminated at roughly the same class-specific depths although they were not as well stratified (Schmidt et al, 1988).…”

“…In a previous report (Schmidt et al, 1988), we found that optic arbors in tectum could be divided into three classes according to the caliber of axon from which they arose (Fig. 1 ).…”