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The Journal of Neuroscience, February 15, 2000, 20(4):1470-1483
Rapid Regulation of Brain-Derived Neurotrophic Factor mRNA
within Eye-Specific Circuits during Ocular Dominance Column
Formation
Edward S.
Lein and
Carla J.
Shatz
Howard Hughes Medical Institute and Department of Molecular and
Cell Biology, University of California, Berkeley, California 94720
The neurotrophin brain-derived neurotrophic factor (BDNF) has
emerged as a candidate retrograde signaling molecule for
geniculocortical axons during the formation of ocular dominance
columns. Here we examined whether neuronal activity can regulate BDNF
mRNA in eye-specific circuits in the developing cat visual system.
Dark-rearing throughout the critical period for ocular dominance column
formation decreases levels of BDNF mRNA within primary visual cortex,
whereas short-term (2 d) binocular blockade of retinal activity with
tetrodotoxin (TTX) downregulates BDNF mRNA within the lateral
geniculate nucleus (LGN) and visual cortical areas. Brief (6 hr to
2 d) monocular TTX blockade during the critical period and also in
adulthood causes downregulation in appropriate eye-specific laminae in
the LGN and ocular dominance columns within primary visual cortex. Monocular TTX blockade at postnatal day 23 also downregulates BDNF mRNA
in a periodic fashion, consistent with recent observations that ocular
dominance columns can be detected at these early ages by physiological
methods. In contrast, 10 d monocular TTX during the critical
period does not cause a lasting decrease in BDNF mRNA expression in
columns pertaining to the treated eye, consistent with the nearly
complete shift in physiological response properties of cortical neurons
in favor of the unmanipulated eye known to result from long-term
monocular deprivation. These observations demonstrate that BDNF mRNA
levels can provide an accurate "molecular readout" of the activity
levels of cortical neurons and are consistent with a highly local
action of BDNF in strengthening and maintaining active synapses during
ocular dominance column formation.
Key words:
critical period; activity-dependent development; neurotrophins; synaptic competition; neural plasticity; cortical
development
Copyright © 2000 Society for Neuroscience 0270-6474/00/2041470-14$05.00/0
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