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The hippocampal formation has been associated with a wide variety of functions including spatial navigation and planning, memory encoding and retrieval, relational processing, novelty detection, and imagination. These functions are dissimilar in terms of their behavioral consequences and modality of representation. Consequently, theoretical standpoints have focused on explaining the role of the hip-pocampal formation in terms of either its spatial or nonspatial functions. Contrary to this dichotomy, we propose that it is essential to look beyond these traditional boundaries between mnemonic and spatial functions and focus instead on the processes that these functions have in common. In this framework, we use electrophysiology data from the spatial domain to predict effects on the systems level, both in spatial and nonspatial domains. We initially outline the results of studies that have used findings from spatial navigation in rodents to predict the patterns of brain activity observable in people who are exploring virtual environments. We discuss how certain properties of space-defining neurons enable space to be represented as a mental map of interconnected locations, which are expressed at multiple spatial scales in separate modules in the hippocampal formation. We then suggest that memories are also organized in networks, characterized by mnemonic and temporal hierarchies. We finish by discussing how virtual-reality techniques can be used to create novel lifelike episodes allowing us to look at episodic memory processes while multivariate analysis tools can be used to explore the organizational structure of mnemonic networks. [ABSTRACT FROM AUTHOR]

How do we know where we are? Orientation in space is key to our daily existence as we follow familiar routes, navigate to a previous location, or just try to get home as quickly as possible. As well as being interesting in its own right, spatial cognition is also a useful model system in which to understand the neural bases of cognition and memory formation more generally. Spatial behavior offers potentially straightforward correlates of neuronal activity that can be studied similarly in adults and infants of both human and non-human animals. The neural mechanisms of spatial behavior can be realistically investigated in a well-controlled way with the aid of virtual reality technologies in humans and rodents. Virtual reality can thus help to bridge the gap between electrophysiological studies in rodents and brain imaging studies using functional magnetic resonance imaging in humans. Within this framework, this article aims to translate findings from the single cell level in rodents to understand the neural and systems level mechanisms of spatial cognition in the human brain. [ABSTRACT FROM PUBLISHER]

Using contextual information to predict aversive events is a critical ability that protects from generalizing fear responses to safe contexts. Animal models have demonstrated the importance of spatial context representations within the hippocampal formation in contextualization of fear learning. The ventromedial prefrontal cortex (vmPFC) is known to play an important role in safety learning, possibly also through the incorporation of context information. However, if contextual representations are related to context-dependent expression of fear memory in humans remains unclear. Twenty-one healthy participants underwent functional MRI combined with a cue-context conditioning paradigm within a self-navigated virtual reality environment. The environment included two buildings (Threat and Safe context), which had distinct features outside but were identical inside. Within each context, participants saw two cues (CS+, CS-). The CS+ was consistently (100% reinforcement rate) paired with an electric shock in the Threat context, but never in the Safe context. The CS- was never paired with a shock. We found robust differential skin conductance responses (SCRs; CS+ ​> ​CS-) in the Threat context, but also within the Safe context, indicating fear generalization. Within the Safe context, vmPFC responses to the CS+ were larger than those in the Threat context. We furthermore found environment-specific representations for the two contexts in the training paradigm (i.e. , before conditioning took place) in the hippocampus to be related to fear expression and generalization. Namely, participants with a weak context representation (z-score < 1.65) showed stronger fear generalization compared to participants with a strong context representation (z-score > 1.65). Thus, a weak neural representation strength of spatial context may explain overgeneralization of memory to safe contexts. In addition, our findings demonstrate that context-dependent regulation of fear expression engages ventromedial prefrontal pathways suggesting this involves a similar mechanism that is known to be involved in retrieval of extinction memory. • Fear generalized to a safe context in a virtual environment. • Increased vmPFC responses to a threat cue in a safe compared to threat context. • Weaker hippocampal context representations predicted fear generalization. [ABSTRACT FROM AUTHOR]