, 2011) to conditionally delete Munc18-1 in the thalamus (ThMunc18KO mice). Like ThVGdKO mice, barrels did not form in the somatosensory cortex of ThMunc18KO mice ( Figures 4A and 4C), see more but cortical lamination was normal at P6 ( Figures 4C–4E). Moreover, ThMunc18KO mice developed cortical lamination defects
at P15 that were similar to those observed in ThVGdKO mice ( Figures 4C, 4D, 4F, and 4H), with cell number and cell density significantly reduced in L4, but significantly increased in L5 ( Figure 4F). Deletion of Munc18-1 had a rather severe effect on thalamic neurons, leading to the death and the eventual degeneration of the somatosensory (VB) thalamus between P0 and P7 ( Figure S4), and the absence of cortical innervation by thalamic axons as demonstrated with VGLUT2 immunostaining ( Figure 4B). This effect was not observed in ThVGdKO mice ( Figures 2B and 2D). Generally, it was difficult
to distinguish L4 from L2/3 and L5 in ThMunc18 mice at P15 ( Figure 4C), although cortical lamination appeared normal in ThMunc18KO somatosensory cortex at P6 ( Figure 4C), as in ThVGdKO mice. The progressive changes in cortical lamination observed in ThVGdKO and ThMunc18KO mice were probably not due to a progressive selleck chemicals llc deletion of Vglut2 or Munc18, because thalamocortical neurotransmission was already absent at P6 in ThVGdKO mice and got no worse thereafter ( Figures 1F and 1G), while thalamocortical neuron degeneration in ThMunc18KO mice occurred between P0 and P7 ( Figure S4). Thus, thalamocortical innervation
had little effect on the initial wave of cortical neuron migration and laminar formation in the first week after birth, although the absence of thalamocortical neurotransmission disrupted barrel formation. We were curious whether the cortical lamination defects observed in ThVGdKO and ThMunc18KO somatosensory cortex were a necessary consequence Ketanserin of abnormal barrel formation, so we also examined cortical laminar development in barrelless mice. Barrelless is a classic mutant with a spontaneous loss-of-function mutation in adenylate cyclase 1 (Adcy1) that causes deficits in thalamocortical synapse development and the complete absence of barrels ( Lu et al., 2003). Unlike ThVGdKO and ThMunc18KO mice, there was no difference in cortical lamination in barrelless mice in comparison to controls ( Figures 4I–4N). These results suggest that cortical lamination defects, as observed in ThVGdKO and ThMunch18KO mice, occur as a consequence of the complete disruption of thalamocortical synaptic communication and are not a necessary consequence of simply disrupting barrel formation. Changes in granular layer development suggest that neuronal differentiation of L4 neurons is disrupted in ThVGdKO mice.
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