In adults information converging on hippocampus from

In adults, information converging on hippocampus from PRC and PHC via entorhinal cortex [ERC] takes two routes through the HIPP, a short route through the monosynaptic circuit with bidirectional ERC←→CA1 connections and a longer route through the trisynaptic circuit (containing DG, CA3). While the short route is available in early infancy with CA1 mature by 2 years of age (Jabés and Nelson, 2015; Lavenex and Banta Lavenex, 2013), it is not until after 18–24 months that DG mossy fibers and CA3 Schaffer collaterals may acquire sufficient maturity for trisynaptic communication from DG and CA3 to the monosynaptic circuit of CA1 and between the hippocampus, parahippocampal gyrus containing PRC and PHC, and neocortex (Ábrahám et al., 2010; Eckenhoff and Rakic, 1991; Lavenex and Banta Lavenex, 2013), structures involved in the formation and retrieval of declarative memories (Nyberg et al., 1996). A seminal study showed that the use of spatial context to guide search for objects emerged in a rudimentary fashion at 24 months in humans, suggesting this as the age at which allocentric, or map-like, representations of space using distal cues could first be used to guide memory for an object\'s location (Newcombe et al., 1998), a key hallmark of hippocampal function (O’Keefe and Nadel, 1978). Other studies have documented 18–24 months as an important transition point for flexible single trial learning, including data to suggest that this is the first point at which children can generalize learned imitation sequences across contexts or remember an object separate from its learning context after a single trial of learning (Robinson and Pascalis, 2004; Meltzoff, 1995). While hippocampal substrates supporting some forms of memory are available earlier in development (e.g., CA1), others are not available until later (e.g., DG/CA3), with substantial continued development between 2 and 5 years and beyond (Lavenex and Banta Lavenex, 2013; Ghetti and Bunge, 2012). Further examination of the behavioral correlates of the monosynaptic short-route and CA1 connections vs. the trisynaptic circuit in transgenic animal models suggested that this route may drive incremental learning of the spatial environment (i.e., Morris Water Maze) without influence of the trisynaptic circuit, whereas the trisynaptic circuit helps to support one trial learning, pattern separation, and spatial tuning of CA1 dihydrofolate reductase inhibitor (Nakashiba et al., 2008). In particular, while processing in DG and CA3 can affect CA1, the bidirectional monosynaptic circuit connecting CA1 and entorhinal cortex does not directly affect DG and CA3. These functional dissociations, coupled with differing rates of development of the two hippocampal circuits, could lead to the early emergence of some memory functions, including early developing competency in tasks with many repetitions or prolonged exposure, but later emergence for the rapid acquisition of fine discriminations between overlapping patterns. Stepping back, the latter set of functions encompasses much of what we consider episodic memory for the day to day events of our lives, as most of what we experience and remember occurs in similar spatial environments often with the same players, just subtle variations in the sequence or timing of activity. In contrast, some cortices adjoining the hippocampus develop early. The PRC at the top of the ventral visual pathway retains memory for objects across 10-s delays in nonhuman primates as young as two weeks of age (Bachevalier et al., 1993). PRC is capable of polymodal binding (Murray et al., 2007), and thus is a candidate for supporting early memory function. PHC, supporting scene memory with input from the dorsal pathway, develops much later (Lavenex and Banta Lavenex, 2013; Golarai et al., 2007). Interestingly, entorhinal cortex, with bi-directional connections between the parahippocampal region (PRC and PHC) and the hippocampus, can form new visuomotor associations without hippocampal input once the basic parameters of a task are acquired (Yang et al., 2014). Yang et al. first trained rhesus macaques to associate one of three objects on a computer screen with a specific location on the screen requiring the animal to touch a specific location. Although it took the animals hundreds of trials to learn the basic task, once they achieved sufficient training they formed new associations between novel objects and the three locations within 30 trials. New learning was impaired when the entorhinal cortex was pharmacologically inactivated but not after inactivation of the hippocampus, demonstrating the contribution of entorhinal cortex to such learning. Layers in entorhinal cortex develop at different rates, with medial entorhinal cortex showing early mature grid cell activity in rats (Wills et al., 2010), and neuronal soma size in superficial layers reaching adult levels by 12 months in humans, potentially supporting early memory function.