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.

Anterior thalamic function is required for spatial coding in the subiculum and is necessary for spatial memory

“…The hippocampal formation lies at the heart of the brain's cognitive mapping capabilities, while also comprising part of an extended system vital for human episodic memory (Spiers et al, 2001;Ranganath and Ritchey, 2012;O'Mara and Aggleton, 2019). The anterior thalamic nuclei (ATN) are key structures within both functional systems (Aggleton and Brown, 1999;Ranganath and Ritchey, 2012).…”

Central Thalamic-Medial Prefrontal Control of Adaptive Responding in the Rat: Many Players in the Chamber

“…Intralaminar lesions that extend into anterior areas of the thalamus produce delay independent impairment of allocentric radial maze DNMTP (Mair et al, 1998), a task spared by intralaminar lesions that do not affect anterior thalamus (Bailey and Mair, 2005; see above). The anterior thalamic nuclei are important nodes in hippocampal-related pathways that support allocentric spatial learning and memory (Aggleton and Nelson, 2015;O'Mara and Aggleton, 2019). Multiple reports indicate that anterior thalamic lesions affect allocentric DNMTP and other measures of spatial memory spared by mPFC, intralaminar, and MD lesions (Warburton et al, 1997;Mair et al, 2003;Wolff et al, 2008).…”

“…Labeled structures include the MD, centrolateral (CL), paracentral (PC), central medial (CM), reuniens (Re), rhomboid (Rh), ventromedial (VM), anterodorsal (AD), anteromedial (AM), anteroventral (AV), interanteromedial (IAM), and paratenial (PT) nuclei and the fornix (f) and mammillothalamic tract (mt). Balleine and O'Doherty, 2010;Chudasama, 2011;Euston et al, 2012;Mitchell et al, 2014;Mair et al, 2015;Marton et al, 2018;Parnaudeau et al, 2018;O'Mara and Aggleton, 2019;Wolff and Vann, 2019;McGinty and Otis, 2020). Vertes et al (2015) classified a group of nuclei along the thalamic midline as limbic based on prominent afferent and efferent connections with limbic-related structures and evidence that they serve limbic-related functions, including affective behaviors, reward-guided responding, response-related working memory, and behavioral flexibility.…”

“…The IAM and AM nuclei are also reciprocally connected to anterior cingulate and prelimbic areas of mPFC (Vertes, 2002;Hoover and Vertes, 2007). Lesions of the anterior thalamic nuclei affect allocentric spatial learning tasks (Aggleton and Nelson, 2015;O'Mara and Aggleton, 2019).…”

Dissociable contributions of mediodorsal and anterior thalamic nuclei in visual attentional performance: A comparison using nicotinic and muscarinic cholinergic receptor antagonists

“…In rodents, the mediodorsal (MD) and anterior thalamic (AT) nuclei have received significant attention due to their distinct cortical inputs. For example, the AT is critical for regulating spatial aspects of memory performance by virtue of its strong hippocampal connections ( O’Mara and Aggleton, 2019 ). In contrast, the MD is thought to be more relevant for executive type functions due to its interactions with the prefrontal cortex (PFC) ( Bueno-Junior et al, 2018 ; Parnaudeau et al, 2015 ).…”