Depletion of Tsc1 or Tsc2 in cultured post-mitotic hippocampal neurons results in increased soma size, decreased dendritic spine density, and increased spine size (Tavazoie et al., 2005). However, loss of Tsc1 in hippocampal neurons in vivo via viral delivery of Cre recombinase, soma size is increased but there is no significant change in spine density (Bateup et al., 2011). On the other hand, Tsc2+/− mice have normal spine density in cortical projection neurons at P19–P20, but increased spine density at P29–P30, suggesting a synaptic pruning defect (Tang et al., 2014). Thus, whereas the effects of Tsc1/2 loss on spine density vary developmentally and across brain regions, soma size is consistently increased.