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Journal of Neuroscience, Vol 8, 945-974, Copyright © 1988 by Society for Neuroscience
Fates of visual cortical neurons in the ferret after isochronic and heterochronic transplantation
SK McConnell
Vision Center Laboratory, Salk Institute for Biological Studies, La Jolla, California 92037.
In the mammalian cerebral cortex, neurons in a given layer are generated at
about the same time in development. These cells also tend to share similar
sets of morphological and physiological properties and have projection
patterns characteristic of that layer. This correspondence between the
birthday and eventual fate of a cortical neuron suggests the possibility
that the commitment of a cell to a particular laminar position and set of
connections may occur very early on in cortical development. The
experiments described here constitute an attempt to manipulate the fates of
newly generated cortical neurons upon transplantation. The first set of
experiments addressed the normal development of neurons in the primary
visual cortex (area 17) of the ferret. Injections of 3H-thymidine into
newborn ferrets showed that neurons generated after birth are destined to
sit in layer 2/3 of the cortex, whereas neurons born on embryonic day (E)
32 populate primarily layers 5 and 6. Many layer 2/3 neurons in adult
ferrets could be retrogradely labeled with HRP from visual cortical areas
18 and 19, while about half of the neurons in layer 6 were found to project
to the lateral geniculate nucleus (LGN). In the second set of experiments,
presumptive layer 2/3 cells were labeled in vivo by injecting ferrets with
3H-thymidine on P1 and P2. Before the cells had a chance to migrate, they
were removed from the donor brain, incubated in a fluorescent dye (DAPI or
fast blue), and dissociated into a single-cell suspension. The labeled
cells were then transplanted into the proliferative zone of a littermate
host ferret ("isochronic" transplants). Over the next few weeks, many of
these dye-labeled cells underwent changes in their position and morphology
that were consistent with a radially directed migration and subsequent
differentiation into cortical neurons. The final positions of
isochronically transplanted neurons in the host brain were mapped out by
using the 3H-thymidine marker after long survival periods. About 97% of
radioactively labeled cells had migrated out into the visual cortex, where
they attained a compact laminar distribution: 99% were found in layer 2/3,
their normal destination. The labeled cells had normal, mostly pyramidal
neuronal morphologies and appeared to be well integrated with host neurons
when viewed in Nissl-stained sections. Ten isochronically transplanted
neurons were successfully labeled after HRP injection into 2 normal target
regions, areas 18 and 19.(ABSTRACT TRUNCATED AT 400 WORDS)
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