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Who gets to define and name a brain area? Can we redefine or change it once a nomenclature is established? And must the definition apply to all species with said structure? When naming a structure, one would want to consider connectivity and cytoarchitectural, molecular, and gross structural features (Amunts & Zilles, 2015), but using any of these alone, or in combination, can lead to confusion in the field when comparing structures across different species, or even within the same species if there is disagreement among investigators. So what about the parts of the hippocampus, which is present in humans and mice, as well as in non-mammalian species (Butler, 2017; Witter et al., 2017)? The definition of area CA2, and even its existence, is perhaps the best example of such a confused state (not to mention that neither CA1 nor CA3 can be properly defined if CA2 is not). In Santiago Ram on y Cajal's drawings of mouse hippocampus, we can see two types of large neurons that are distinct from the small pyramidal neurons we now recognize as those in CA1, yet still lacking the characteristic thorny excrescences of CA3 neurons: some appearing to be receiving input from the dentate gyrus, and some that do not (Ram on y Cajal, 1909) (Figure 1a). However, the area of CA2 was first coined with the other cornu ammonis (CA) regions by Lorente de N o (1934) (Figure 1b); CA2 neurons, by his definition, were the large neurons lacking the mossy fiber input. The lack of clarity, then, lies with the definition: can neurons in CA2 ever receive input from the dentate gyrus granule neurons via the mossy fibers if the definition precludes it? Many of Ram on y Cajal's cells—those receiving mossy fiber input yet lacking thorny excrescences—might have been forgotten had it not been for a newer, molecular definition of CA2 that took hold among researchers studying hippocampal gene expression (e.g., PCP4, bFGF, and NT3) and appeared to include both populations of Ram on y Cajal's cells (Lein et al., 2005; Phillips et al., 1990; Woodward et al., 1992; X. Zhao et al., 2001). Although some earlier works investigated CA2 neurons in electrophysiological and anatomical studies (Bartesaghi & Ravasi, 1999; Chevaleyre & Siegelbaum, 2010; Mercer et al., 2007; M. Zhao et al., 2007), it was only when the mossy fiber synapses were studied in combination with staining for PCP4, STEP, and RGS14 did the field have to contend with the definition of CA2 itself (Dudek et al., 2016; Kohara et al., 2014). The molecular markers simply did not align with the definition of Lorente de N o's CA2 (again, the large neurons lacking the mossy fiber input): most of the neurons that Kohara found staining for PCP4, STEP, and RGS14 did have mossy fiber input in this case, although with decidedly smaller synapses in the stratum lucidum than those in CA3 (Kohara et al., 2014). As yet, no molecular marker has been identified that clearly distinguishes between the CA2 neurons receiving mossy fibers, and those in Lorente de N o's CA2 that do not, yet the absence or presence of mossy fibers suggests that there are two distinct populations of CA2 neurons. When the axonal branching patterns of individual neurons from these two populations were examined, however, they appeared not to differ from each other (in this case, the authors referred to neurons as being in CA2 and CA3a') (Tamamaki et al., 1988). Thus, it is this molecular (i.e., labeling with PCP4, STEP, or RGS14) definition of CA2 that is now in common use by investigators using rodents in their studies. Nevertheless, labeling for these CA2 protein markers is not identical to each other. In this Special Issue, several manuscripts address this very topic. For example, Radzicki et al. (2023) directly compare the staining patterns for several commonly used CA2 markers (e.g., PCP4, STEP, and RGS14) at different levels along the dorsal-ventral axis in an effort to establish which ones delineate best CA2's borders with CA1 and CA3 in mice. In addition, they build on the work by Kohara et al. to further characterize the mossy fiber synapses within this molecularly defined CA2. What is not evident in most stains, though, is that in mice the mossy fibers appear to make a turn within CA2 to traverse in the dorsal to ventral direction (Kohara et al., 2014; Radzicki et al., 2023). In a second contribution to the Special Issue, Bienkowski discusses their efforts to define CA2 molecularly using an approach based on combined gene expression data and connectivity (Bienkowski, 2023). In his commentary, he describes the Hippocampus Gene Expression Atlas (HGEA), which attempts to reconcile some of the conflicting boundaries presented in different brain atlases (Bienkowski et al., 2018; Lein et al., 2007). Key issues addressed in the commentary are possible reasons why the Allen Institute's mouse brain atlas does not list a CA2 in the ventral hippocampus (Lein et al., 2007), and whether there is evidence of cellular heterogeneity within the CA2. Chevaleyre and Piskorowski (2023) also discuss the topic of cellular heterogeneity in this issue, but do so with attention to different gradients within CA2— both across the transverse axis (i.e., moving in the direction from the distal, CA1 side, to proximal, CA3 side, toward the dentate gyrus) and across the radial axis (i.e., moving from the stratum oriens [deep] side of the pyramidal cell layer to the stratum radiatum [superficial] side). One such gradient in CA2 in the transverse axis is described here by Radzicki et al. (2023) who showed that staining for the perineuronal nets (PNNs) with Wisteria floribunda agglutinin was stronger in the distal-most CA2 (CA1 side) than in the proximal (CA3) side of CA2. Although more quantitative studies would be needed to confirm this Accepted: 31 January 2023