Contributions of Early Versus Later-Generated Cortical Layers to the Development of Laminar Patterns in Ferret Somatosensory Cortex

Abstract

Abstract : The inside-out sequence of generation and formation of the cortical layers is well documented and has been observed in many species. While it is recognized that the early-generated components of cerebral cortex are essential for the formation of important architectural structures, the contributions of later generated cortical layers have not been completely addressed. This study examines the role of individual cortical layers in the development of the cortical laminae by disrupting the formation of specific cortical layers with the antimitotic methylazoxymethanol (MAM). Chapter 1 introduces the ferret as a model for studying key aspects of cortical development, and presents findings from birthdating studies that determined the timing of final mitosis and migration for cortical neurons in each layer of the ferret somatosensory cortex. The findings from these experiments were used to target the formation of specific cortical layers through timed in utero injections of MAM. Chapter 2 presents findings that layer 4 formation is dismpted after in utero injections of MAM on embryonic day 33 (E33). Treatment with MAM on E33 resulted in a greatly reduced thickness of layer 4, and reduced density of neurons within the remaining layer 4. Neuronal genesis resumed after E33 MAM treatment; neurons generated after the treatment migrated to appropriate locations and the overall laminar pattems of somatosensory cortex were preserved. Chapter 3 reports findings from experiments that further explore the ability of cortical cells to migrate in E33 MAM-treated cortex. Cortical precursor cells obtained from the ventricular zone of normal ferrets were transplanted into organotypic slices prepared from both layer 4-dismpted and normal ferret neonates.