Although the neurons of the hippocampal formation have been studied in detail within the context of information storage, a better way of thinking about this subcortical region is that it is a pathway that transmits information between the outside world and the neocortex for long-term storage; this information once consolidated in the neocortex can be retrieved and combined with the real-time sensory information of an animal to execute optimal behavioral responses (Clark et al. 2002; Marr 1971; Mölle and Born 2009; Qin et al. 1997; Squire 1992, 2009). In adult humans, the volume of the grey matter (bilaterally) of the hippocampus ranges from ~ 6.0 to 7.0 cm3 and the volume of the grey matter of the neocortex ranges from ~ 600 to 860 cm3, a 100-fold difference (Suzuki et al. 2005). As well, the hippocampus has 0.1 billion neurons and the neocortex has 16 billion neurons, a 160-fold difference (Andrade-Moraes et al. 2013; Herculano-Houzel 2009; Simić et al. 1996). These differences certify that evolution has devoted much less neural space to the consolidation and retrieval of information by the hippocampus than to the long-term storage of information within the neocortex. A comparable difference is expected for other vertebrates (Footnote 1, Murray and Wise 2011; Murray et al. 2017), and this difference has likely existed since the Cambrian explosion half a billion years ago, which included fish (Ovsepian and Vesselkin 2014), during which time the ‘continents’ presumably had little terrestrial life.

Before the advent of GPS, taxi drivers who were required to memorize the road maps of a large metropolitan area, e.g., London, were found to have an enlarged grey-matter volume of the hippocampal formation (Maguire et al. 2000, 2009). The hippocampus transfers declarative information (e.g., sensory impressions, visual objects, read or written text, etc.) over a period of weeks and months of training before finalizing the consolidation process in the neocortex (Kim, Thompson et al. 1995; Maviel, Bontempi et al. 2004; Marr 1971; Squire 1992; Takahara et al. 2003; Wang, Frankland et al. 2009). Also, the extent of retrograde amnesia following hippocampal damage varies as a function of how much tissue is removed, such that removal of the entire hippocampus that includes the temporal lobes can produce a 40-to-50-year retrograde amnesia in humans (Squire, Knowlton et al. 2001). The idea that the hippocampus mediates the consolidation of declarative information is well-accepted, and it is understood that part of this process occurs during sleep and during quiet immobility (Berger and Thompson 1978; Clark et al. 2009; Corkin 2002; Chroback and Buzsaki 1994,1996; Girardeau et al. 2009; Girardeau and Zugaro 2011, 2014; Hoffman and Berry 2009; Kim et al. 1995; Kudrimoti and McNaughton 1999; Logothetis et al. 2012; Marr 1971; Maviel et al. 2004; O’Keefe and Nadel 1978; Ólafsdóttir et al. 2017; Pavlides and Winson 1989; Rolls 2004; Roy et al. 2017; Schacter et al. 2008; Scoville and Milner 1957; Siapas and Wilson 1998; Squire and Knowlton 2000; van Vugt et al. 2018; Wilson and McNaughton 1994). During both slow-wave sleep and REM sleep, learned events are replayed in sequence such that during slow-wave sleep they are replayed in compressed time, and during REM sleep they are replayed in real-time (Boyce et al. 2016; Girardeau et al. 2009; Louie and Wilson 2001; Wilson and McNaughton 1994), and this memory replay occurs throughout the neocortex (of humans, Dickey et al. 2022; Huber, Tononi et al. 2004), thereby globalizing the stored information. And not only is declarative information consolidated during sleep (and quiet wakefulness), but motor routines typically associated with cerebellar function are also consolidated (Schiller, Phelps et al. 2010; Søgård, Monoach et al. 2024; Vorster and Born 2015). This should not be surprising since, under normal circumstances, sensation and movement occur together (Schiller and Tehovnik 2015). While learning (which occurs during wakefulness), the neural activity of the hippocampus, neocortex, and the cerebellum are found to be rhythmically coordinated in animals including humans (i.e., theta activity is synchronized but not always in phase between the regions, Bush, Burgess et al. 2017; Hoffman and Berry 2009; Wikgren et al. 2010). During periods of memory replay, the hippocampus and neocortex of primates are very active, while the cerebellum is suppressed (Logothetis et al. 2012). Finally, the genes that mediate neural plasticity for myelination and synaptogenesis are turned on during sleep, but this activity occurs in both the neocortex and the cerebellum (as illustrated in rodents, Cirelli, Tononi et al. 2004). Summarized is a schematic of the hippocampal formation and its connections to the neocortex and subcortex (Figure 1).

So, just how does the hippocampus mediate consciousness? Patient HM, who had severe damage of his hippocampal formation, was conscious in terms of being able to perceive the outside world in its entirety using all his senses, and in being able to engage in continuous dialogue with another person (Corkin 2002). But when he was required to narrate his childhood story, he at best delivered incomplete fragments of information, as though to have just a ‘photo-album’ impression of his parents. This conclusion has now been bolstered by observations of many other patients with hippocampal damage. Hassabis et al. (2007b) had hippocampal patients construct an imagined experience as triggered by a visual cue. For example, when asked to imagine being on a beach, patient PO3 said, “Really, all I can see is the colour of the blue sky and the white sand, the rest of it, the sounds and things, obviously I’m just hearing.” By comparison a hippocampal-intact individual said, “It’s very hot and the sun is beating down on me. … I can hear the sounds of small wavelets lapping on the beach. … Behind me is a row of palm trees.”. This difference is reminiscent of the types of experiences evoked by electrical stimulation of the temporal lobes in human subjects, whereby the report is also very fragmented and devoid of detail and most importantly, always the same between different bouts of stimulation (Penfield 1975). Moreover, when narrating stories, the hippocampal formation becomes very active as verified with fMRI, suggesting that the hippocampus is engaged in the retrieval of information, namely, in the spatial reconstruction of scenes for storytelling (Hassabis et al. 2007a).

Much has been made by brain-computer interface enthusiasts about hooking up two neocortical hemispheres for the purpose of communicating information between two individuals (Pais-Vieira, Nicolelis et al. 2013; but also see Tehovnik, Teixeira-e-Silva 2014). What is clear is that for such communication to be non-fragmented consciously, the enthusiasts would first need to pass all the information through a hippocampal homologue to string together the information that is stored willy-nilly in each person’s neocortex. In fact, attempts have been made to produce a hippocampal interface in both rodents and primates that could serve such a function if extended to long-term information storage (see: Berger, Deadwyler et al. 2011; Deadwyler, Berger et al. 2016).

Summary:

1. The hippocampal formation is a pathway that consolidates and retrieves declarative information in the neocortex by linking the sensory world to the cognitive world as an animal learns.

2. The consolidation process occurs during sleep and during alert immobility.

3. Declarative information is consolidated at the same time as is motor information, which is consistent with the idea that sensation and movement occur together and therefore should not be partitioned.

4. The hippocampal formation’s role in consciousness is to string together the information housed in the neocortex, so that it can be communicated (in logical order) to the outside world.

5. Brain computer interfaces of the future will need to string together the information that is scattered through the neocortex, before it can be meaningfully interpreted by a receiver.

Footnote 1: In nonmammalian vertebrates, such as fish, amphibians, reptiles, and birds, the telencephalon contains a neocortical homologue and the hippocampus (Murray et al. 2017).

Figure 1: (A) The innervation pattern (external loops) of the hippocampal formation (of one side) is illustrated. The base of the hippocampus is composed of the CA1 pyramidal fibres and the subiculum. This region sends projections to the neocortex via the cingulate cortex and to the basal forebrain via the septum. From the septum, fibres are sent toward the prefrontal cortex, basal forebrain, and brain stem. The source of the hippocampal information originates from the neocortex, basal forebrain, and the brain stem carrying sensory (including interoceptive) information. (B) The internal loop of the hippocampal formation is composed of the entorhinal cortex (ER), the dentate gyrus (DG), CA3 pyramidal fibres, CA1 pyramidal fibres, and the subiculum (Sub). Afferent input and pyramidal output are indicated.