Development of the motor system: Hopping rats produced by prental irradiation

Abstract

Irradiation of prenatal and infant rats resulted in a spectrum of highly reproducible nervous system malformations associated with locomotor abnormalities difficult to correlate with morphologic findings. Fetal rats exposed to 150 R on the 13th, 14th, or 15th day of gestation were born with a hopping gait, paired hind and forelimbs moving in unison instead of the normal alternating mode. Some animals switched partly or completely to an alternating gait of forelimbs, rarely hind limbs. Rats irradiated on the 12th, 16th, or 17th day did not hop. The problem: Was the hopping related to the brain or spinal cord? Hopping rats could jump to a level or tilted landing platform. Their forelimbs tactually placed independently of each other, whether they hopped or not, but the hind limbs scratched synchronously. Thoracic cord transection led to crossed extension hind-limb reflexes in normal rats, and simultaneous withdrawal of hind limbs in hopping rats, in response to bilateral pinprick. The dorsal horns, especially Rexed's laminae I-VI, and sometimes the most dorsal part of VII, which were being formed in the 13- to 15-day period as shown by tritiated thymidine autoradiography, were underdeveloped. This was due to failure to make restitution of residual dorsal proliferative cells remaining after radiation. Some neurons destined for the dorsomedial parts of the ventral horns may have been lost after the 13th- and 14th-day irradiation, but not the 15th. Precisely how dorsal horn deficiencies could affect the spinal locomotor generator, presumed to be more ventrally situated, it is not yet known. Nor has the exact nature of the suprasegmental adaptation to the hopping mechanism and switching to normal forelimb gait been worked out.