Effects of cytotoxic deletions of somatic sensory cortex in fetal rats.
Pregnant rats were injected on the 14th day of gestation with the cytotoxic drug methylazoxymethanol acetate. This compound causes the death of neural precursor cells that were synthesizing DNA at the time of injection. After birth, the progeny of treated mothers grew to maturity with a neocortex that was greatly reduced in area by the death of all cells, particularly at the frontal and occipital poles but at medial and lateral margins of neocortex as well. In the remaining cortex layers II through IV failed to develop. The experiment deprived growing thalamocortical axons, which innervate the somatic sensory cortex late in development, of part of their normal target area and of a substantial number of their definitive target cells. It also deprived them of any cues they might have received from these target cells migrating through them as the axons accumulate beneath the cortical plate. Anatomical experiments indicated that, despite these defects, thalamocortical axons could still colonize the sensorimotor areas and form synapses in their typically bilaminar pattern, though the outer, denser lamina of terminations occurred abnormally at the level of the apices of layer V pyramidal cell bodies. Receptive field mapping of single and multiunit responses in the somatic sensory region showed brisk responses and receptive fields of normal size. It also indicated the formation of a body map that was topographically intact except for deletions at its periphery; that is, a total map was not compressed into a smaller area. This suggests that somatic sensory thalamocortical fibers recognize only remaining cortical target cells in appropriate fields. Moreover, successful ones among them seem to recognize neighborhood relations and conserve synaptic space at the expense of those that would have innervated the deleted peripheral parts of the area. Pyramidal neurons in the remaining cortical layers and in ectopic islands of cells that had incompletely migrated from the neuroepithelium, probably on account of destruction of radial glial cell precursors, were shown by retrograde labeling to send their axons only to appropriate subcortical targets. Pyramidal neurons, though recognized as such, also adopted a variety of abnormal orientations, such as inversion, apparently in an attempt to grow apical dendrites toward major zones of synaptic terminations.
D000818:Animals; D001369:Axons / Q000502:physiology / Q000648:ultrastructure; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000187:drug effects; D003712:Dendrites / Q000648:ultrastructure; D005260:Female; D008746:Methylazoxymethanol Acetate / Q000009:adverse effects; D009474:Neurons / Q000648:ultrastructure; D011247:Pregnancy; D011712:Pyramidal Tracts / Q000648:ultrastructure; D051381:Rats; D011919:Rats, Inbred Strains; D013003:Somatosensory Cortex / Q000196:embryology / Q000502:physiology* / Q000648:ultrastructure; D013569:Synapses / Q000648:ultrastructure; D013788:Thalamus / Q000502:physiology / Q000648:ultrastructure
D008746:Methylazoxymethanol Acetate