The Journal of Neuroscience, May 15, 2001, 21(10):3542-3548
Analysis of the Activity-Deprived Zebrafish Mutant
macho Reveals an Essential Requirement of Neuronal
Activity for the Development of a Fine-Grained Visuotopic Map
Lara
Gnuegge1,
Susanne
Schmid2, and
Stephan C. F.
Neuhauss1
1 Max-Planck-Institut für Entwicklungsbiologie,
72076 Tübingen, Germany, and 2 Zoologisches Institut,
Universität Tübingen, 72076 Tübingen, Germany
The formation of a retinotopic map is thought to involve an
activity-independent molecular phase for early steps of both axon pathfinding and projection and a later phase in which cross talk between retinal ganglion cells (RGCs) and tectal neurons modifies and
refines the neuronal connections. We report that the maturation of the
retinotopic map in the zebrafish tectum involves activity-dependent processes. Zebrafish larvae mutant for the gene macho
(mao) lack neuronal activity in RGCs and also display an
enlarged retinotectal projection field but no significant increase in
single axon length. This morphological defect can be phenocopied by
raising larvae under TTX-induced neural impulse blockade. The effect of
activity deprivation is dependent on the developmental stage. The
projection phenotype in mao as well as in the
TTX-treated larvae develops between 4 and 6 d post-fertilization
(dpf), after complete tectal coverage is first achieved.
Electrophysiological recordings of RGCs in wild-type and
mao zebrafish larvae reveal a temporally regulated
reduction of sodium current in the mutant between 5 and 6 dpf. This
coincides with the time of the axonal projection shifting on the tectum
to compensate for the disparate growth patterns of the retina and the
tectum. Our genetic and physiological analyses suggest a model in which
neuronal activity in RGCs is needed for the establishment of
morphological plasticity.
Key words:
visual system; retinotectal projection; sodium currents; zebrafish; axon guidance; plasticity; Danio rerio; retinal
ganglion cell; TTX
Copyright © 2001 Society for Neuroscience 0270-6474/01/21103542-07$05.00/0