Progressive behavioral changes during the maturation of rats with early radiation-induced hypoplasia of fascia dentata granule cells

Abstract

Localized exposure of the neonatal rat brain to X-rays produces neuronal hypoplasia specific to the granule cell layer of the hippocampal dentate gyrus. This brain damage causes locomotor hyperactivity, slowed acquisition of passive avoidance tasks and long bouts of spontaneous turning (without reversals) in a bowl apparatus. Here we report how these behavioral deficits change as a function of subject aging and behavioral test replications. Portions of the neonatal rat cerebral hemispheres were X-irradiated in order to selectively damage the granule cells of the dentate gyrus. The brains of experimental animals received a fractionated dose of X rays (13 Gy total) over postnatal days 1 to 16 and control animals were sham-irradiated. Rats between the ages of 71–462 days were tested 3 separate times on each of the following 3 behavioral tests: 1) spontaneous locomotion, 2) passive avoidance acquisition, and 3) spontaneous circling in a large plastic hemisphere. Rats with radiation-induced damage to the fascia dentata exhibited long bouts of slow turns without reversals. Once they began, irradiated subjects perseverated in turning to an extent significantly greater than sham-irradiated control subjects. This irradiation effect was significant during all test series. Moreover, in time, spontaneous perseverative turning was significantly potentiated in rats with hippocampal damage but increased only slightly in controls. Early radiation exposure produced locomotor hyperactivity in young rats. While activity levels of controls remained fairly stable throughout the course of the experiment, the hyperactivity of the irradiated animals decreased significantly as they matured. The total distance traveled by irradiated rats was significantly above sham-irradiated controls at the beginning of the study but was significantly lower than controls at the conclusion. Young, irradiated rats learned a passive avoidance task more slowly than controls. They not only took more trials to meet criterion but their latency to move into an area in which they had just been shocked was significantly shorter than sham-irradiated rats. Passive avoidance learning improved in mature animals. These data suggest that radiation-induced damage to the fascia dentata produces task-dependent behavioral deficits that change as a function of subject age and/or behavioral testing.