Disruption of layers 3 and 4 during development results in altered thalamocortical projections in ferret...

The precision of projections from dorsal thalamus to neocortex are key toward understanding overall cortical organization and function. To identify the significance of layer 4 cells in receiving the bulk of thalamic projections in somatosensory cortex, we disrupted layer 4 genesis and studied the effect on thalamic terminations in ferrets. Second, we ascertained the result of layer 4 disruption on functional responses and topographic organization. Methylazoxy methanol (MAM) was injected into pregnant ferrets on embryonic day 33 (E33), when most layer 4 neurons of somatosensory cortex are generated. This treatment resulted in dramatic reduction in the thickness of targeted layer 4. E38 MAM treatment was used as a control, when layer 2-3 neurons are generated. The projections of ventrobasal thalamus into somatosensory cortex were studied using DiI injections. We found only subtle differences between groups (normal, E33, or E38 MAM-treated) in the thalamic afferent pattern on postnatal day 1 (P1) and P7. On P14, thalamic terminations distribute almost equally throughout the remaining cortical layers in the E33 MAM-treated group compared with normal and E38 MAM-treated animals, in which the ventrobasal thalamus projects primarily to central layers. Electrophysiological recordings conducted on mature ferrets treated with MAM on E33 demonstrated that somatotopic organization and receptive field size are normal. These findings emphasize the importance of layer 4 in determining the normal laminar pattern of thalamic termination and suggest that, although its absence is likely to impact on complex neocortical functional responses, topographic organization does not arise from the influence of layer 4.