Developmental profile of tissue plasminogen activator in postnatal Long Evans rat visual cortex

PURPOSE To investigate the distribution, expression, and activity of tissue plasminogen activator (tPA) in the visual cortex of the Long Evans rat during postnatal development, and to explore the relationship between tPA levels and the critical period of visual cortical plasticity. METHODS Long Evans rats of either sex (n=131) were divided by postnatal age in weeks (PW) into five groups: PW1 (6-8 days, before eye opening, n=19), PW3 (20-22 days, beginning of critical period, n=28), PW5 (34-36 days, later stage of critical period, n=28), PW7 (48-50 days, end of critical period, n=28), and PW14 (95-100 days, adult, n=28). The distribution and expression of tPA was detected using immunofluorescence histochemistry and western blot analysis, respectively. tPA activity in the visual cortex was determined using a chromogenic assay kit. RESULTS tPA-containing cells were mostly located in visual cortex layer II-III and layer IV during postnatal development. In layer II-III the density of tPA-containing cells reached peak at PW 5, and then reduced to minimum at PW14. In layer IV and V-VI, the density of tPA-containing cells reached a maximum at PW3, and then decreased to the minimum at PW14. Western blot analysis indicated that tPA was detected in visual cortex of rats from PW3 onwards with the highest quantity present at PW5. By comparison, the peak in tPA activity occurred slightly earlier at PW3, and then decreased steadily to lower levels at PW14. CONCLUSIONS The critical period of visual cortical plasticity, which occurs in early postnatal life, correlates well with tPA expression in the rat visual cortex. This suggests that the expression of tPA is produced in sufficient amounts to balance the increase of chondroitin sulfate proteoglycan expression, at the same time blocking its function, thus allowing synaptic modification to continue. tPA activity may be one of the factors influencing the duration of the critical period and underlying the heterogeneity of synaptic plasticity between visual cortex layer II-III and layer IV.