Space and Memory (Far) Beyond the Hippocampus: Many Subcortical Structures Also Support Cognitive Mapping and Mnemonic Processing

Abstract

Memory research remains focused on just a few brain structures—in particular, the hippocampal formation (the hippocampus and entorhinal cortex). Three key discoveries promote this continued focus: the striking demonstrations of enduring anterograde amnesia after bilateral hippocampal damage; the realization that synapses in the hippocampal formation are plastic e.g., when responding to short bursts of patterned stimulation (“long-term potentiation” or LTP); and the discovery of a panoply of spatially-tuned cells, principally surveyed in the hippocampal formation (place cells coding for position; head-direction cells, providing compass-like information; and grid cells, providing a metric for 3D space). Recent anatomical, behavioral, and electrophysiological work extends this picture to a growing network of subcortical brain structures, including the anterior thalamic nuclei, rostral midline thalamic nuclei, and the claustrum. There are, for example, spatially-tuned cells in all of these regions, including cells with properties similar to place cells of the hippocampus proper. These findings add new perspectives to what had been originally been proposed—but often overlooked—half a century ago: that damage to an extended network of structures connected to the hippocampal formation results in diencephalic amnesia. We suggest these new findings extend spatial signaling in the brain far beyond the hippocampal formation, with profound implications for theories of the neural bases of spatial and mnemonic functions.