Expression of constitutively active p21H‐ras^val12 in postmitotic pyramidal neurons results in increased dendritic size and complexity

Abstract

The small G protein p21Ras is a critical molecular switch for relaying neurotrophic actions and is essential for normal functioning and plasticity of the nervous system. In this study, the morphogenetic effects of p21Ras were investigated on neurons in vivo. Morphological changes of layers II/III and Vb commissural pyramidal neurons of the primary somatosensory cortex were analyzed in transgenic mice expressing permanently active p21H-RasVal12 in postmitotic neurons. Pyramidal cells were retrogradely labelled with biotinylated dextran amine and subsequently traced using Neurolucida. Compared with wild-type mice, transgenic animals showed a significant increase in the surface area and volume of basal dendrites on the proximal and intermediate segments in layers II/III and on further distal segments in layer V. In addition, the surface area and volume of the trunk and of the proximal segments of oblique branches of apical dendrites were enlarged in both layers. Sholl analyses of basal and apical dendrites showed a significant increase in dendritic complexity of layer V neurons. A positive correlation was observed between the size of the basal dendrite and the neuronal soma size in the transgenic population, indicating that growth-promoting effects of p21H-RasVal12 affect both cellular compartments in parallel. However, the dendritic surface correlated with the number of tips and dendritic stem diameter in both wild-type and transgenic populations, demonstrating that these relations represent rather conservative design principles in dendritic morphology. The data presented here suggest an important role of p21Ras-dependent signaling in the final differentiation and maintenance of dendritic morphology.

Scaling properties of pyramidal neurons in mice neocortex

“…In a previous study, a striking increase of dendritic tree size was verified in the pyramidal neurons of synRas mice neocortex [4]. Surface area and volume of proximal and intermediate dendritic segments were significantly augmented which was caused mainly by increased dendritic diameter, and not by segment elongation.…”

“…The volume of the neocortex of synRas mice is expanded up to 25% as compared to wildtype mice. In particular cortical pyramidal neurons express the synRas construct at high levels resulting in a dramatically enlarged volume of the cortical pyramidal cells which is mainly caused by increased dendritic diameter and tree degree [4,5]. The number of neurons, however, remains unchanged [3].…”

Cluster Analysis of Cortical Pyramidal Neurons Using SOM

“…In Ref. [2], we found that the volume of the neocortex of synRas mice is expanded up to 25% as compared to wildtype mice. This is due to the dramatically enlarged volume of the cortical pyramidal cells caused mainly by increased dendritic diameter and tree degree, whereas the number of neurons remains unchanged.…”

“…The details of experimental procedures have been described in [2]. The main deliverables were two sets of retrogradely labelled pyramidal cells (28 cells from wildtype and 28 cells from transgenic mice) which were reconstructed ( Fig.…”

“…Thicker sections allowed only ambiguous tracing of thinner dendritic branches. Shrinkage correction was carried out in the z axis, but not in the xy plane, because shrinkage was negligible in these dimensions [2].…”