From previous developmental studies, it has been proposed that the neurons of the ventrolateral cortex, including the primary olfactory cortex, differentiate from progenitor cells in the lateral ganglionic eminence. The objective of the present study was to test this hypothesis. The cells first generated in the forebrain of the rat migrate to the surface of the telencephalic vesicle by embryonic day (E) 12. Using [3 H]thymidine, we found that most of these cells contributed to the formation of the deep layer III of the primary olfactory cortex. To study the migratory routes of these cells, we made localized injections of the carbocyanine fluorescent tracers DiI and DiA into various parts of the lateral ganglionic eminence in living embryos at E12-E14 and subsequently maintained the embryos in a culture device for 17-48 hr. After fixation, most migrating cells were located at the surface of the telencephalic vesicle, whereas others were seen coursing tangentially into the preplate. Injections made at E13 and in fixed tissue at E15 showed that migrating cells follow radial glial fibers extending from the ventricular zone of the lateral ganglionic eminence to the ventrolateral surface of the telencephalic vesicle. The spatial distribution of radial glial fibers was studied in Golgi preparations, and these observations provided further evidence of the existence of long glial fibers extending from the ventricular zone of the lateral ganglionic eminence to the ventrolateral cortex. We conclude that cells of the primary olfactory cortex derive from the lateral ganglionic eminence and that some early generated cells migrating from the lateral ganglionic eminence transgress the cortico-striatal boundary entering the preplate of the neocortical primordium.

Along with tufted cells, mitral cells are the principal projection neurons in the olfactory bulb (OB). During the development of the OB, mitral cells migrate from the ventricular zone to the intermediate zone, where they begin to send axons along the lateral olfactory tract (LOT) to the cortical olfactory zones. Subsequently, they lose their tangential orientation, enabling them to make contact with the axons of the olfactory sensory neurons (OSN) that innervate the whole OB. Here, we investigated the distinct morphological features displayed by developing mitral cells and analyzed the relationship between the changes undertaken by these neurons and the arrival of the OSN axons. Immunostaining for specific markers of developing axons and dendrites, coupled with the use of fluorescent tracers, revealed the morphological changes, the continuous reorientation, and the final refinement that these cells undergo. We found that some of these changes are dependent on the arrival of the OSN axons. Indeed, we identified three main chronological events: 1) newly generated neurons become established in the intermediate zone and project to the LOT; 2) the cells reorient and spread their dendrites at the same time as OSN axons penetrate the OB (this is a sensitive period between embryonic day (E)15-16, in which the arrival of afferents establishes a spatial and temporal gradient that facilitates protoglomerulus and glomerulus formation); and 3) final refinement of the radially orientated cells to adopt a mature morphology. These results suggest that both afferent inputs and intrinsic factors participate to produce the well-defined sensory system.

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We have described our studies of the development of projections from layer 5 of the rat neocortex to subcortical targets in the midbrain and hindbrain. The major points are briefly summarized here. 1. Layer-5 neurons extend a primary axon out of cortex and along a spinally directed trajectory, bypassing all of their targets in the midbrain and hindbrain. These targets are later contacted exclusively by collaterals formed by a delayed interstitial branching of the primary axon, not by growth cone bifurcation. 2. Collateral branches only form at stereotypic positions, not randomly along the length of the axon. Thus, specific cues identify branch points, and the length of the primary axon well behind its growth cone responds to these cues. 3. Layer-5 neurons in diverse areas of cortex initially develop the same basic set of collateral branches, although they will permanently retain different subsets of the initial common set. Therefore, branch cues are recognized by layer-5 neurons independent of whether the collateral projection formed is functionally appropriate for the cortical region in which the neuron resides. 4. In vitro and in vivo evidence indicates that one of the major branches, which forms the corticopontine projection, is induced and directed into its target, the basilar pons, by a diffusible, target-derived, tropic signal. Thus, a chemotropic cue promotes recognition of the basilar pontine target by the primary layer-5 axons. 5. In this system, then, target selection is not the responsibility of the growth cone of the primary axon.(ABSTRACT TRUNCATED AT 250 WORDS)