Fig. 2

The hippocampus and its connections. (a) The hippocampus lies in the medial temporal lobes; it is connected to several subcortical (connections indicated in red) and cortical structures (connections indicated in grey). The major neocortical input to the hippocampus comes from the perirhinal and postrhinal cortices through the entorhinal cortex (EC). The medial entorhinal cortex (MEC) receives a major input from the postrhinal cortex (the rodent homolog of the parahippocampal cortex of primates) which is connected to the visuospatial areas of the parietal lobe; it brings to the hippocampus visuospatial information (VSI) (“where” pathway). On the other hand, the lateral entorhinal cortex (LEC) receives its primary input from perirhinal cortex, which carries object-related information (ORI) (“what” pathway).The visual input from the eyes is conducted through the occipital cortex. The auditory input is conducted through the temporal lobe and the somatosensory system is related to the parietal cortex. This sensory system circuit constitutes the main input of information to the hippocampus, through EC. The subiculum (Sb) is considered the major output region of the hippocampus: it sends projections to other areas of the subicular complex (pre/parasubiculum), to the thalamus, hypothalamus and septum (via fornix), as well as to the deep layers of the EC. On the other hand, CA3 projects mainly to the lateral septum [122] and receives an input mainly from medial septum [232]. Amygdala is related with emotions, playing a role in the memory circuit in associating desire with objects/spatial locations [21]. Amygdala projects to thalamus that in turn projects back to the neocortex, activating the appropriate behavioural output. Brain areas that have been reported to contain place-related neural activity are grey (reviewed by [110]).E encoding, R retrieval, PL place recognition, R/C retrieval/consolidation, VSI visuospatial information (“Where”); ORI object-related information (“What”) (b) The hippocampus has the same basic structure in humans, non-human primates and rodents. In the tri-synaptic circuit the information flows from layer II in the Entorhinal cortex (EC) made up of the Medial and Lateral Entorhinal Cortex (MEC and LEC) to granule cells in the DG through Perforant Pathway (Lateral Perforant Pathway; LPP and Medial Perforant Pathway; LPP) and then from the granule cells to the CA3 pyramidal cells through the Mossy Fibres (MF), from the CA3 pyramidal cells to the CA1 pyramidal cells through the Schaffer Collaterals (SC) and finally from the CA1 pyramidal cells to the subicular pyramidal cells that in turn project to deep layers of the EC. Additionally, the pyramidal cells of EC send axons directly to CA3 (through the perforant pathway) and to CA1 (through the temporoammonic pathway-TP). The most numerous excitatory input in CA3 arise from the recurrent collaterals (RC). pyramidal cells—glutamatergic excitatory transmission and GABAergic inhibitory transmission granular cells—essentially glutamatergic