In the rat, the proximal–distal plane revealed opposing gradients of inputs to the rat anteroventral nucleus and anteromedial nucleus (Figures 2.3 and 2.6C), with inputs to the rat medial mammillary nucleus showing a third pattern. The majority of mammillary body projections from the septal hippocampus arose from the central subiculum while more distal inputs arose from the temporal subiculum (Figure 2.6A, B). Anteromedial thalamic projections in the rat originated predominantly from the proximal subiculum, along a steep gradient, whereas anteroventral projections originated mainly from distal subiculum, showing the reverse gradient. Mammillary body projections were positioned between the two - mostly in the second-most proximal region.
The more distal tendency of anteroventral nucleus projections from the subiculum was also found by Ishizuka (2001). The proximal-distal gradients found here also fit with other, previous findings of a proximal-distal divide for anterior thalamic nuclei projections in the rat (Meibach and Seigel, 1975, Wright et al., 2010). However, here the slope of the gradient within this structure has been quantified using four divisions,
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revealing a steady increase from proximal to distal subiculum for anteromedial projections and vice versa for anteroventral projections. Moreover, although
mammillary body efferents were found in more superficial layers and throughout the septal-temporal extent of the subiculum in previously outlined research in the rat (Meibach and Siegel, 1975; Witter et al., 1990; Wright et al., 2010), the graded proximal-distal nature of these projections has not previously been analysed. This gradient is of particular interest in this study as mammillary body outputs showed a high preference for the central two subdivisions of the subiculum, which was largely
positioned between the anteromedial and anteroventral output sites.
In the rat, the proximal subiculum projections to the anteromedial nucleus overlap with the sources of inputs to the lateral entorhinal cortex, perirhinal cortex and prelimbic cortex (Aggleton, 2012; Ishizuka, 2001; Jay and Witter, 1991; Kloosterman et al., 2003; Naber and Witter, 1998; Naber et al., 2000; Witter et al., 2000a, b). Unlike the
anteromedial thalamic connections, these hippocampal-cortical projections also originate from distal CA1. Based on these interactions, e.g. with the perirhinal cortex and lateral entorhinal cortex, the rat proximal subiculum might be expected to
preferentially process object-based information (Ahn and Lee, 2015; Bussey and Saksida, 2007; Diana et al., 2007; Witter et al., 2000a, b). In contrast, the rat distal subiculum is more closely connected with the medial entorhinal cortex and postrhinal cortex, regions containing positional and navigational information (Burwell and Hafeman, 2003; Fyhn et al., 2004; Hafting et al., 2005).
The evidence for a functional proximal-distal gradient in the rat remains, at present, preliminary, with most support coming from electrophysiological studies. The two principal cell types in the rat subiculum are “bursting” and “spiking”, names that reflect
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their electrophysiological properties (O’Mara, 2005). The distribution of bursting cells seems to remain positioned relative to the apical dendrites, whereas the axons of spiking cells have a more widespread dispersal in the transverse plane (Witter, 2006). A study from Kim and Spruston (2012) looked at the relationship between patterns of firing and target location in subicular neurons. Their results showed that, in line with previous observations, the distal subiculum projected predominantly to medial entorhinal cortex, retrosplenial cortex, and ventromedial hypothalamus, and consisted mainly of bursting neuronal cell types (~80%), while the opposite was true for proximal projections to lateral entorhinal cortex, nucleus accumbens, and orbitofrontal cortices, which consisted mainly of spiking neuronal cell types (~80%). Amidst these were projections to
thalamic nuclei arising from intermediate subiculum, of which 50% were likely to be bursting neurons. The likelihood maps of bursting versus spiking neurons along the transverse plane projecting to their efferent targets are consistent with previous electrophysiological findings of these cell types.
Moreover, cells with spatial firing properties are found in the subiculum. Place firing by subiculum cells shows more coherence in the distal subiculum, associated with higher firing rates than the proximal subiculum (Sharp and Green, 1994). A complementary study from Kim et al. (2012) once more revealed a proximal-distal gradient in the subiculum in terms of sparse to dense firing rates, coding spatial representations. The proximal subiculum displayed sparse, canonical firing rates, but moving towards distal subiculum the firing rates became higher and more distributed. The authors inferred that the distributed spatial representation in the subiculum carries more information about spatial location and contextual cues than the sparse representations in CA1. More indirect evidence comes from the finding that proximal CA1 activity (most closely
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interlinked with distal subiculum) has greater spatial resolution than distal CA1 (most closely interlinked with proximal subiculum; Henriksen et al., 2010).
Preliminary evidence for the complementary gradient (object-based processing in the proximal subiculum) comes from the differential activity of distal CA1 cells, as measured by Arc expression, for nonspatial learning (Nakamura et al., 2013; see also Hunsaker et al., 2008). Caution is, however, required as some electrophysiological studies of subicular spatial cells, e.g. boundary vector cells and place cells, have failed to find proximal-distal differences (Brotons-Mas et al., 2010; Lever et al., 2009).
In contrast to the rodent proximal-distal topography along the subiculum, the macaque subiculum showed similar profiles of label in the proximal-distal plane for all of the diencephalic targets examined. The greatest number of projections consistently arose from the more distal (R3) subiculum (Figures 2.4, 2.10 and 2.12). Support for this finding comes from a study that also placed retrograde tracers in the anteromedial nucleus of macaque monkeys (Xiao and Barbas, 2002b). Again, the distal subiculum was depicted as the major source of hippocampal inputs, with projections to the
anteromedial nucleus present along the full anterior-posterior axis of the hippocampus. Intriguingly, that same study described some additional anteromedial thalamic inputs from CA3 (Xiao and Barbas, 2002b), something not observed in the present material.
Yet, anatomical proximal-distal topographies do exist in the monkey hippocampus for other connections. Examples already mentioned include how the proximal subiculum (and distal CA1) contain the majority of projections to prefrontal cortex, amygdala and nucleus accumbens, as well as connections with the perirhinal and rostral entorhinal cortices (Aggleton, 1986; Blatt and Rosene, 1998; Insausti and Munoz, 2001; Saunders
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and Rosene, 1988; Suzuki and Amaral, 1990; Van Hoesen et al., 1979; Witter and Amaral, 1991). In contrast, the distal subiculum is preferentially interconnected with both caudal and lateral entorhinal cortex, as well as the parahippocampal areas TH and TF (Aggleton, 2012). These connections would again seem to provide a potential distinction between object based (proximal) and scene- or context-based (distal) connections within the monkey subiculum (Diana et al., 2007; Murray et al., 2007; Ritchey et al., 2015). Unlike rats, however, the majority of inputs to the medial diencephalon consistently arose from the distal half of the monkey subiculum, suggesting a bias towards scene- or context-based information.
2.4.3 Longitudinal (anterior-posterior/septal-temporal) axis of the subiculum