Brain Struct Funct (2011) 216:301–317 305 Krieg (1946) and Blackstad (1956), which may in part explain the lack of attention to its possible existence. cell generation is superimposed on the ‘‘inside-out’’ pattern (Angevine 1965; Bayer 1980; Smart 1982). Development Neurogenesis of hippocampal pyramidal cells occurs mainly during gestational days 17–19 in rats (Schlessinger et al. 1978; Bayer 1980) and days 14–16 in mice (Angevine 1965; Caviness 1973; Stanﬁeld and Cowan 1979a; Smart 1982). CA1 pyramidal cells that originate at particular times during these periods are found at speciﬁc radial locations in the cell layer of the adult animal, following the ‘‘inside-out’’ pattern typical for other cortical areas. Neu- rons formed early are found at depth in the cell layer. Cells generated later form the dense superﬁcial band of pyra- mids. The situation is somewhat more complex in CA3 due to the extended route of migration of pyramidal cells from their ventricular germinative zone to the developing extraventricular part of CA3 (Altman and Bayer 1990). A proximal (early) to distal (late) pattern of CA3 pyramidal CA1 Morphological differences between cells at different radial locations in the pyramidal cell layer and the maintenance of spatial relations according to neuronal birthdays may still be accommodated within the idea that the pyramidal cells are a radially homogeneous population of neurons. However, a migration defect in reeler mice does not result in a simple ‘‘inside-out’’ to ‘‘outside-in’’ reversal. Neither does this mutation result in the random scattering of cells that is observed for the dentate granule cells. Instead pyramidal cells are sorted, according to their time of generation, into two, more or less distinct, sublayers (Fig. 3a–e; Caviness 1973; Stanﬁeld and Cowan 1979a, b; Deller et al. 1999; Coulin et al. 2001). Early born cells concentrate in a layer close to the alveus. This layer is separated by a cell-sparse zone from a layer formed by lately born cells closer to the obliterated hippocampal ﬁssure. Fig. 3 a Hippocampus of a mouse carrying the Relnorl reelin mutation. b Two distinct cell layers and deep cell clusters in the septal mid-proximodistal CA1 of a Relnorl mouse. c At more temporal levels packing densities and cell sizes in the two CA1 layers resemble those in normal laboratory mice. d CA1 pyramidal cells in Relnorl mouse retain their neurochemical identity with regard to calbindin, with only the younger, now deep pyramids showing moderate calbindin immunoreactivity. e The two CA1 layers of Relnorl mice do not show appreciable differences in their parvalbumin immunoreac- tivity. f Zbtb20 (green) in C57Bl/6 mouse superﬁcial pyramidal cells and Sox5 (red) in deep pyramidal cells. g Scattered deep pyramidal cells in distal CA3 of the Chincilla do not receive mossy ﬁber input close to their soma. h Scattered deep pyramidal cells in distal CA3 of the fox. Scalebars a 0.5 mm, b–h 50 lm. The original of f was kindly provided by Prof. Niels A. Jensen (Nielsen et al. 2010, with permission of Oxford University Press) 123