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Journal of Neuroscience, Vol 10, 1197-1216, Copyright © 1990 by Society for Neuroscience
NMDA receptor agonist and antagonists alter retinal ganglion cell arbor structure in the developing frog retinotectal projection
HT Cline and M Constantine-Paton
Biology Department, Yale University, New Haven, Connecticut 06511.
The development of sensory maps is thought to require an activity-
dependent structural rearrangement of afferent terminal arbors within the
CNS which recreates the topographic relations of sensory somata present in
the periphery. In the frog retinotectal projection, activation of the NMDA
receptor plays a role in this structural plasticity. Exposure of the optic
tectum of tadpoles to NMDA receptor antagonists results in a rearrangement
of retinal ganglion cell arbors so that their organization into a
topographic projection and eye- specific stripes is disrupted (Cline et
al., 1987; Cline and Constantine-Paton, 1989). Exposure of the optic tectum
to the receptor agonist, NMDA, increases the eye-specific segregation of
these arbors (Cline et al., 1987). We examined the projection of the
supernumerary retina and the morphology of individual retinal afferent
arbors of untreated, NMDA-treated, APV-treated, MK801-treated, and
MK801/NMDA- treated 3-eyed tadpoles and young postmetamorphic frogs in an
effort to understand how NMDA receptor activation is involved in the growth
and ordering of retinal arbors. Treatments with MK801 in combination with
NMDA resulted in a desegregation of eye-specific stripes, whereas
treatments with MK801 or NMDA alone did not. As reported previously, APV
treatment resulted in stripe desegregation without increasing the
tangential area (measured from 2-dimensional drawings) of the terminal
arbors. However, a detailed analysis revealed that the APV-treated tadpole
arbors have 35% reduction in branch density (branch tips/area) compared to
untreated 3-eyed tadpole arbors. We treated the optic tectum with a range
of concentrations of NMDA prepared in the slow- release plastic Elvax. NMDA
at 10(-4) M in Elvax was the optimal concentration to produce the
sharpening of stripe borders. Exposure of the tectum to NMDA at 10(-6) M in
Elvax produced no change in the stripe pattern, while 10(-2) M NMDA in
Elvax resulted in beading of the arbors. At the optimal concentration NMDA
treatment results in a 75% reduction in the number of axons crossing from a
stripe to an interstripe zone. Drawings of individual HRP-labeled,
NMDA-treated arbors demonstrate that they have fewer branch points and
fewer branch tips. NMDA treatment reduced arbor density by approximately
50%. Arbors drawn from untreated postmetamorphic frogs have twice the
branch density of arbors from untreated tadpoles. NMDA treatment in these
animals reduced the branch density by 55%, comparable to the reduction seen
in tadpole branch density. Our data support a specific hypothesis for NMDA
receptor involvement in the activity-dependent structural refinement
process within the developing retinotectal projection.(ABSTRACT TRUNCATED
AT 400 WORDS)
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