A role for subplate neurons in the patterning of connections from thalamus to neocortex

Abstract

During cerebral cortical development, ingrowing axons from different thalamic nuclei select and invade their cortical targets. The selection of an appropriate target is first evident even before thalamic axons grow into the cortical plate: initially axons accumulate and wait below their cortical target area in a zone called the subplate. This zone also contains the first postmitotic neurons of the cerebral cortex, the subplate neurons. Here we have investigated whether subplate neurons are involved in the process of target selection by thalamic axons by ablating them from specific cortical regions at the onset of the waiting period and examining the subsequent thalamocortical axon projection patterns. Subplate neurons were ablated at the onset of the waiting period by intracortical injections of kainic acid. The effect of the ablation on the thalamocortical projection from visual thalamus was examined by DiI-labeling of the LGN days to weeks following the lesion. At two to four weeks post-lesion, times when LGN axons would have normally invaded the cortical plate, the axons remained below the cortical plate and grew past their appropriate cortical target in an anomalous pathway. Moreover, examination of LGN axons at one week post-lesion, a time when they would normally be waiting and branching within the visual subplate, indicated that the axons had already grown past their correct destination. These observations suggest that visual subplate neurons are involved in the process by which LGN axons select and subsequently grow into visual cortex. In contrast, subplate neurons do not appear to play a major role in the initial morphological development of the LGN itself. Subplate ablations did not alter dendritic growth or shapes of LGN projection neurons during the period under study, nor did it prevent the segregation of retinal ganglion cell axons into eye-specific layers. However, the overall size of the LGN was reduced, suggesting that there may be increased cell death of LGN neurons in the absence of subplate neurons. To examine whether subplate neurons beneath other neocortical areas play a similar role in the formation of thalamocortical connections, subplate neurons were deleted beneath auditory cortex at the onset of the waiting period for auditory thalamic axons. Subsequent DiI labeling revealed that in these animals the majority of MGN axons had grown past auditory cortex instead of innervating it. Taken together these observations underscore a general requirement for subplate neurons throughout neocortex in the process of cortical target selection and ingrowth by thalamic axons.(ABSTRACT TRUNCATED AT 400 WORDS)