Normal development of embryonic thalamocortical connectivity in the absence of evoked synaptic activity.
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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.
