Functional organization of the hippocampal longitudinal axis

Abstract

The precise functional role of the hippocampus remains a topic of much debate. According to a dominant view, the dorsal/posterior hippocampus is implicated in memory and spatial navigation and the ventral/anterior hippocampus mediates anxietyrelated behaviours. However, this 'dichotomy view' may need revision. Gene expression studies demonstrate multiple functional domains along the hippocampal long axis, which often exhibit sharply demarcated borders. By contrast, anatomical studies and electrophysiological recordings in rodents suggest that the long-axis is organized along a gradient. Together, these observations suggest a model in which functional long-axis gradients are superimposed on discrete functional domains. This model provides a potential framework to explain and test the multiple functions ascribed to the hippocampus.The hippocampus is a medial temporal lobe structure critically involved in episodic memory and spatial navigation [1][2][3][4][5][6][7] . Its long, curved form is present across all mammalian orders and runs along a dorsal (septal) to ventral (temporal) axis in rodents, corresponding to a posteriorto-anterior axis in humans (FIG. 1a-b). The same basic intrinsic circuitry is maintained throughout the long axis and across species (FIG. 1c). Despite this conserved intrinsic circuitry, the dorsal and ventral portions have different connectivities with cortical and subcortical areas, and this has long posed a question as to whether the hippocampus is functionally uniform along this axis. Here we review cross-species data that show how the seemingly disparate functions ascribed to the hippocampus can be accommodated by a model in which different functional properties exist along the longitudinal axis.The severe memory impairment suffered by patient H.M. following bilateral hippocampal resection 1 led to intensive study 8 of patients and animal models with hippocampal damage, with an ensuing characterisation of hippocampal function in terms of declarative memory 2 , encompassing both episodic and semantic memory. At the same time, however, evidence emerged for a hippocampal role in spatial memory, based on the discovery of hippocampal 'place cells' 9,10 and the demonstration that hippocampal lesions impair spatial memory 4 . Both the declarative memory hypothesis 11 and the spatial mapping hypothesis 12 of hippocampal function proposed a unitary model in which the entire hippocampus is dedicated

The influence of hippocampal atrophy on the cognitive phenotype of dementia with Lewy bodies

“…However, other pathologies may contribute to the cognitive symptoms of DLB and should be investigated further; one study has previously observed that cognitive decline in LBD may be a consequence of alpha‐synuclein, amyloid‐beta and phosphorylated tau pathology (Howlett et al, 2015), and additionally, one study of the medial temporal lobe showed that alpha‐synuclein pathology, rather than AD pathology, had a role in the atrophy of the amygdala (Burton et al, 2012). Hippocampal volume showed the strongest association with the CAMCOG memory score, which is in keeping with the memory function of the hippocampus (Eichenbaum, 2004; Strange et al, 2014). These results also indicate that atrophy to adjacent medial temporal lobe subregions can also influence the DLB cognitive phenotype, with an overlap of symptoms: parahippocampal surface thickness was associated with CAMCOG cognition and memory subscores, but not executive function, the entorhinal surface thickness was associated with total CAMCOG scores, as well as CAMCOG memory and executive function subscores.…”

Topographic separation of fornical fibers associated with the anterior and posterior hippocampus in the human brain: An MRI‐diffusion study

“…In contrast, more posterior hippocampal projections in the fornix include the dense inputs to the mammillary bodies (Christiansen, Dillingham, et al., 2016). It should, however, be emphasized that in the rat and macaque brains these distinctions are relative, that is, there is a gradient in the anterior–posterior inputs from the subiculum and CA1 rather than a sharp division between the anterior and posterior hippocampus (Aggleton, 2012; Barbas & Blatt, 1995; Evensmoen et al., 2015; Kjelstrup et al., 2008; for review see Strange et al., 2014). …”

“…Of the two areas, the anterior hippocampus has been more linked to stress, anxiety, and emotional processing (Bannerman et al., 1999; Chase et al., 2015; O'Mara, 2005), whereas the posterior hippocampus is more typically linked to fine‐grain spatial processing (Poppenk et al., 2013; Strange et al., 2014). These differences do not, however, reflect a dichotomy, rather a gradation of change along the anterior–posterior axis (Collin et al., 2015; Poppenk et al., 2013; Strange et al., 2014). One interpretation is that the anterior hippocampus is important for forming large‐scale representations of the environment, whereas the posterior hippocampus provides more detailed representations (Poppenk et al., 2013; Strange et al., 2014).…”

“…Despite the role of this tract in cognition, surprisingly little is understood about the organization of the fibers within the human fornix and how this might relate to its various connections. The principal motivation to examine their topography arises from the growing evidence for functional differences along the anterior–posterior axis of the hippocampus (Collin, Milivojevic, & Doeller, 2015; Fanselow & Dong, 2010; Poppenk, Evensmoen, Moscovitch, & Nadel, 2013; Strange, Witter, Lein, & Moser, 2014). For instance, evidence from functional neuroimaging studies suggests a role of the posterior hippocampus in spatial navigation (e.g., Hartley, Maguire, Spiers, & Burgess, 2003), whereas anterior hippocampus has been associated with goal‐directed spatial decision making (Viard, Doeller, Hartley, Bird, & Burgess, 2011).…”

“…A similar organization exists in the rat, whereby fibers from the temporal hippocampus (equivalent to the primate anterior hippocampus) are located more laterally within the fornix, whereas fibers from the more septal hippocampus (equivalent to the posterior hippocampus) are found more medially (Swanson & Cowan, 1977; Wyss, Swanson, & Cowan, 1980). It is not yet known if the human fornix has a similar topography, even though such information could provide a useful means to compare the respective functions of the anterior and posterior hippocampal networks (Aggleton, 2012; Strange et al., 2014). …”