The Journal of Neuroscience, December 1, 2002, 22(23):10313-10323
Normal Development of Embryonic Thalamocortical Connectivity in
the Absence of Evoked Synaptic Activity
Zoltán
Molnár1, *,
Guillermina
López-Bendito1, *,
Juan
Small1,
L. Donald
Partridge3,
Colin
Blakemore2, and
Michael C.
Wilson3
1 Department of Human Anatomy and Genetics, University
of Oxford, Oxford, OX1 3QX, United Kingdom, 2 University
Laboratory of Physiology, University of Oxford, Oxford, OX1 3PT, United
Kingdom, and 3 Department of Neurosciences,
University of New Mexico Health Sciences Center, Albuquerque, New
Mexico 87131
This study is concerned with the role of impulse activity and
synaptic transmission in early thalamocortical development. Disruption
of the gene encoding SNAP-25, a component of the soluble N-ethylmaleimide-sensitive factor attachment protein
(SNAP) receptor complex required for regulated neuroexocytosis,
eliminates evoked but not spontaneous neurotransmitter release
(Washbourne et al., 2002). The Snap25 null mutant mouse
provides an opportunity to test whether synaptic activity is required
for prenatal neural development. We found that evoked release is not
needed for at least the gross formation of the embryonic forebrain,
because the major features of the diencephalon and telencephalon were normal in the null mutant mouse. However, half of the homozygous mutants showed undulation of the cortical plate, which in the most
severely affected brains was accompanied by a marked reduction of
calbindin-immunoreactive neurons. Carbocyanine dye tracing of the
thalamocortical fiber pathway revealed normal growth kinetics and
fasciculation patterns between embryonic days 17.5 and 19. As in normal
mice, mutant thalamocortical axons reach the cortex, accumulate below
the cortical plate, and then start to extend side-branches in the
subplate and deep cortical plate. Multiple carbocyanine dye placements
in the cortical convexity revealed normal overall topography of both
early thalamocortical and corticofugal projections.
Electrophysiological recordings from thalamocortical slices confirmed
that thalamic axons were capable of conducting action potentials to the
cortex. Thus, our data suggest that axonal growth and early topographic
arrangement of these fiber pathways do not rely on activity-dependent
mechanisms requiring evoked neurotransmitter release. Intercellular
communication mediated by constitutive secretion of transmitters or
growth factors, however, might play a part.
Key words:
thalamus; cortex; mouse; carbocyanine dyes; synaptogenesis; synaptic activity; SNAP-25
*
Z.M. and G.L.-B. contributed equally to this work.
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