Projection neurons and interneurons in the lateral geniculate nucleus undergo distinct forms of degeneration ranging from retrograde and transsynaptic apoptosis to transient atrophy after cortical ablation in rat

The cytological responses of thalamic interneurons to selective degeneration of thalamocortical projection neurons after cortical damage in the adult brain are poorly understood. We used a unilateral neocortical lesion model (occipital cortex ablation) in the adult rat to test the hypothesis that interneurons and projection neurons in the lateral geniculate nucleus undergo distinct forms of degeneration. In situ nuclear DNA fragmentation in neurons in the lateral geniculate occurs maximally at 7 days postlesion. Geniculocortical projection neurons that are identified by the retrograde tracer Fluorogold die primarily with a morphology of endstage apoptosis prominent at 7 days postlesion. In contrast, interneurons, identified by their particular nuclear ultrastructure and by glutamic acid decarboxylase immunoreactivity, undergo an atrophic vacuolar pathology starting early during the period of projection neuron death and peaking after the projection neuron death is complete. This degeneration of interneurons is transient, because these neurons exhibit structural recovery and their numbers are not changed significantly postlesion. A rare subset of interneurons (less than one in 100 interneurons and less than one in 100 apoptotic cells) undergoes apoptosis concurrently with the projection neurons. We conclude that different types of neurons within the same thalamic nucleus respond differently to focal cortical target deprivation. Unlike the apoptosis-prone projection neurons, most interneurons undergo transient transsynaptic atrophy and recovery rather than cell death. Nevertheless, a small subset of lateral geniculate interneurons undergoes transsynaptic apoptosis in response to projection neuron apoptosis. The pathological responses of thalamic neurons to cortical trauma vary depending on cell type. (C) 2002 IBRO. Published by Elsevier Science Ltd. All rights reserved.