312 Brain Struct Funct (2011) 216:301–317 Fig. 6 Examples of particularly interesting histoarchitectural, con- nectional, neurochemical and pathological ﬁndings that distinguish superﬁcial and deep pyramidal cells of CA1. The cell layer has been drawn to resemble the different appearances of the layer along both the septotemporal and proximodistal axis in mouse and rat. In other species much of CA1 is dominated by a histoarchitectural phenotype that encompasses only a narrow segment of the variations seen in rat and mouse similar views were still expressed by Rose (1926) and Abbie (1938). Only with Krieg (1946) does ‘‘the subiculum carr[y] the reduction of layers to its logical conclusion— only one layer remains’’, which continues compacted into the hippocampus. The number of layers present is actually not of primary importance—neither is their degree of homology to layers in other cortical areas. At issue is an acknowledgement of layering, which in time may generate the data necessary to decide on their number and relation to the cortex. Distinct output streams or parts of translaminar functional units? Deep and superﬁcial pyramidal cells may merely represent distinct output streams of the hippocampus. However, beyond differences in cellular phenotypes, cortical lami- nation implies functional interactions between layers. Are there interactions between pyramidal cells in the sublayers, and, if so, how are they mediated? Current evidence sug- gests that pyramidal-pyramidal cell connections within CA1 are sparse as compared to neocortical areas or CA3 (Deuchars and Thomson 1996). Tract tracing studies also suggest weak associational pathways in CA1 (Amaral et al. 1991; Swanson et al. 1978). After some developmental pruning (Aniksztejn et al. 2001), they are limited to stratum oriens of the adult rat (Amaral et al. 1991; Tamamaki et al. 1987). A restricted distribution along the longitudinal and transverse axis of CA1 (Swanson et al. 1978), with axon branches of a CA1 pyramidal cell most prominent among its basal dendrites (Tamamaki et al. 1987), suggests pri- marily local, patch-like associational interactions, which may help create local cellular ensembles of the type described by, e.g., Eichenbaum et al. (1989) or Nakamura et al. (2010). An alternate way of local interactions may be the local dendritic or somatic electrotonic coupling of pyramidal 123 cells (Andrew et al. 1982; Nu´n˜ez et al. 1990; Baimbridge et al. 1991; Mercer et al. 2006), which has been a matter of discussion ever since its ﬁrst description (Knowles et al. 1982; Bennett and Pereda 2006). In a more recent incar- nation, evidence for axo-axonal coupling of cells has also been presented (Schmitz et al. 2001). Of note are evidence for an activity-dependent incidence of coupling (Perez- Velazquez et al. 1994; Church and Baimbridge 1991; Perez Velazquez and Carlen 2000) and the participation of both superﬁcial and deep cells in coupled groups, which did lead Baimbridge et al. (1991) to suggest that they represent a functional unit. An activity/state-dependent coupling of distinct output streams seems possible. Proximity is a key determinant in the likelihood of two cells to be connected, and the degree to which pyramidal cells condense into a compact layer may regulate this type of interaction phylogenetically. Where to go next An immediate step forward would be to go back to existing data. During our review, we have occasionally seen illus- trations that suggest layers within CA1 or CA3, but that without support in writing remained inconclusive. Since expectation may tint perception, reviewing existing data for evidence of sublayers may be worthwhile. The array of natural mutations and transgenic mice that exhibit lami- nation ‘‘defects’’ may facilitate the deﬁnition of the ana- tomical and physiological phenotypes of deep and superﬁcial pyramidal cells. The selective expression of GFP in a subset of pyramidal cells that belongs to a neu- rochemically deﬁned group in thy1-GFP (M line) or in other sparsely GFP expressing mouse lines offer direct access to the characterization of their physiological and connective properties in comparison with non-expressing cells using the approaches outline by Kajiwara et al. (2008) and used so effectively by Deguchi et al. (2011). The