310 vulnerability of superﬁcial cells to focal injections of low doses of c-acetylenic GABA (Goodman 1998), an indirect excitotoxin, which attenuates the formation of kynurenate and GABA and which produces selective cell death also in other parts of the hippocampal formation (Wu and Schw- arcz 1998). Additional evidence for distinct afferent connections of superﬁcial and deep CA1 pyramidal cells is provided by Bannister and Larkman (1995), who showed that, in the rat, deep pyramidal cells extend less of their dendritic tree into stratum radiatum than superﬁcial pyramidal cells. A sig- niﬁcantly higher apical dendritic aborization of superﬁcial pyramidal cells in comparison with cells located at deeper levels was also observed in macaque monkeys (Altemus et al. 2005). In the rat, relative position alone does not explain this distribution pattern as deep pyramidal cell are able to extend dendrites into the stratum moleculare to a similar extent as superﬁcial pyramidal cells (Bannister and Larkman 1995). Differences in dendritic arborizations suggest differences in afferent connectivity because intrin- sic and extrinsic hippocampal afferents show differences in their predilection to terminate either in the stratum oriens or the stratum radiatum (van Groen and Wyss 1988). The precise patterns of distribution also relate to septo-temporal and proximo-distal relations between the sources of intrin- sic afferents in CA3 and their targets in CA1 (Ishizuka et al. 1990). While it is unlikely that either deep or superﬁcial cells are exclusive targets of parts of the intrinsic afferent circuitry, quantitative differences in the sourcing of affer- ents from speciﬁc septotemporal and proximodistal hippo- campal levels should exist. Experimental support for this idea comes from two studies of intrinsic afferents of the reeler mouse CA1 and the morphology of the pyramidal cells located in the two cell tiers. Tracings of commissural ﬁbers by Borrell et al. (1999) show a preference for these ﬁbers to terminate above the superﬁcial tier of cells. Only few dendrites of deep pyramidal cells extend into this layer (Deller et al. 1999), and superﬁcial pyramids should be the primary targets of these ﬁbers. In the Guaira spiny rat, which resembles the Parma wallaby and fox in the histoarchitecture of the pyramidal cell layer, the dendritic length of pyramidal cells located within the stratum oriens exceed that of more superﬁcial pyramidal cells by a factor two (Scorza et al. 2011), sug- gesting a phylogenetic regulation of not only the sourcing but also the number of inputs of superﬁcial and deep pyramids. Differences in the extent of the dendritic trees of rat superﬁcial and deep pyramidal cells have also been described for CA3 (Fitch et al. 1989), however, with a higher arborization of the dendrites of superﬁcial pyrami- dal cells both superﬁcial and deep to the pyramidal cell layer. 123 Brain Struct Funct (2011) 216:301–317 Although not directly concerned with the radial posi- tion of pyramidal cells, the ﬁndings of Deguchi et al. (2011) in mice sparsely expressing GFP also provide evidence for different intrinsic connections of superﬁcial and deep pyramidal cells. The authors show that pyra- midal cell generated during a particular time window in CA3 preferentially connect with a developmentally mat- ched set of CA1 pyramids. In addition, the interconnected cell populations are characterized by distinct gene expression patterns. The ﬁndings were thought to repre- sent functional streams, which actually begin already in the dentate gyrus. As the time of pyramidal cells origin also determines their radial position, superﬁcial and deep cells should belong to different streams, and it is tempting to think that the histoarchitectural differentiation of the pyramidal cell layer is a structural reﬂection of such functional streams. Physiology Normal physiology Unless speciﬁed otherwise, data mentioned in the fol- lowing were obtained in laboratory rats or mice. In vitro, calbindin expression has been found to abolish post-tetanic potentiation in hippocampal neurons (Chard et al. 1995) and intracellular calcium antagonizes the NMDA-type glutamate receptors (Koh and Choi 1994). Considering the differences in calbindin content and the differential distribution of deep and superﬁcial pyramidal dendrites (Bannister and Larkman 1995), one may expect that the stimulation of basal dendrites would be more efﬁcient in eliciting NMDA receptor-dependent LTP than the stimu- lation of apical dendrites. A number of reports indicate that this is indeed the case (Capocchi et al. 1992; Kaibara and Leung 1993; Leung and Shen 1995; Arai et al. 1994). NMDA receptor-independent apical and basal LTP exhi- bit few if any differences in naive hippocampal slices but are instead differentially affected by calcium channel blockers and tyrosine kinase inhibitors (Cavus and Teyler 1998). A differential responsiveness of cells may also be reﬂected in the preferential expression of the immediate early genes c-Fos and JunB in deep pyramidal cells fol- lowing context dependent memory retrieval (Strekalova et al. 2003, their Fig. 2). Also, contextual fear conditioning and extinction upregulate c-Fos and extracellular signal regulated kinase (Erk) in distinct populations of CA1 pyramidal cells (Tronson et al. 2009) with seemingly dif- ferent radial distributions. Two classes of pyramidal cells could also be deﬁned based on their gamma ﬁring phases during theta oscillations (Senior et al. 2008), and it was