Transsynaptic cell death of neurons following striatopallidal lesions does not occur in substantia nigra pars reticulata in developing rats.

Abstract

In adult rats, combined lesions of the striatum and globus pallidus (GP) cause transsynaptic cell death of neurons in the substantia nigra pars reticulata (SNr) which becomes apparent 1-2 weeks after the lesions. This delayed cell death of SNr neurons has been explained to be caused by over-excitation of SNr neurons which results from an imbalance between excitatory and inhibitory inputs due to two simultaneous events: acceleration of the excitatory input from the disinhibited subthalamic nucleus (STN) and deprivation of the inhibitory input from the striatum. To examine whether the transsynaptic neuronal death in SNr is caused by the same lesions in developing rats, we destroyed the striatum and GP in rats on postnatal days 10 (P10), P15, P20, P25, P30, P35 and P60 by injecting ibotenic acid. We found that cell death did not occur in SNr neurons in rats younger than P20 and that Fos expression induced in STN neurons after these striatopallidal lesions in P10 and P20 rats was lower than that in P30 or P60 rats. These findings suggest that excitation of STN neurons is not enough to cause cell death of SNr neurons in rats younger than P20. Immature functional connection between the cerebral cortex and STN in the early developing animals may contribute to the resistivity of SNr neurons to transsynaptic delayed cell death.