Time to retire the serial Papez circuit: Implications for space, memory, and attention

Abstract

After more than 80 years, Papez serial circuit remains a hugely influential concept, initially for emotion, but in more recent decades, for memory. Here, we show how this circuit is anatomically and mechanistically naïve as well as outdated. We argue that a new conceptualisation is necessitated by recent anatomical and functional findings that emphasize the more equal, working partnerships between the anterior thalamic nuclei and the hippocampal formation, along with their neocortical interactions in supporting, episodic memory. Furthermore, despite the importance of the anterior thalamic for mnemonic processing, there is growing evidence that these nuclei support multiple aspects of cognition, only some of which are directly associated with hippocampal function. By viewing the anterior thalamic nuclei as a multifunctional hub, a clearer picture emerges of extra-hippocampal regions supporting memory. The reformulation presented here underlines the need to retire Papez serially processing circuit.

Keywords: Amnesia; Attention; Context; Hippocampus; Mammillary bodies; Memory; Space; Thalamus.

Fig. 1

A) Schematic of the principal connections described by Papez (1937) that constitute a serial circuit for the experience of emotions. B) Updated schematic depicting major, direct interconnections between the sites in Papez circuit, based on axonal tracing data from the rat and nonhuman primate. The schematic also provides information on the pathways linking these structures. Blue arrows, fibres in mammillothalamic tract; green arrows, fibres in fornix; purple arrows, fibres in cingulum bundle; red arrows, fibres in internal capsule. (Note that the parahippocampal projections to the rat anterior thalamic nuclei join the internal capsule, while the corresponding projections in the macaque involve the fornix). Abbreviations: MTT, mammillothalamic tract.

Fig. 2

Blue arrows show principal connections of the anteromedial (AM), red arrows the anteroventral (AV), and green arrows the anterodorsal (AD) thalamic nucleus. The black dashed arrows refer to potentially important connections not directly involving the anterior thalamic nuclei (ATN). The thickness of the arrows reflects differences in the density of the projections. The panel to the right provides a thumbnail of key connections. Abbreviations: HD, presence of head-direction units (in parenthesis if lower frequency); θ, theta modulated cells; Place, place cells; impairments in the Morris water maze at encoding (E), consolidation (C), retrieval (R) (from Safari et al., 2020). Other abbreviations: AC, anterior cingulate; HPC, hippocampal formation; LMB, lateral mammillary nucleus; MPF, medial prefrontal cortex; MMB, medial mammillary nucleus; MPF, medial prefrontal cortex; PHC, parahippocampal region; RSP, retrosplenial cortex.

Fig. 3

Activity-dependent synaptic plasticity in parallel, interacting circuits supports memory consolidation across three distinct but interacting locales: a temporal lobe memory stream; a medial diencephalic memory stream; and sites of cortico-cortical memory consolidation. Note, retrosplenial cortex also projects to the hippocampus, via the parahippocampal region. Diamonds indicate previously-observed sites of synaptic plasticity; other synapses remain to be comprehensively investigated.

Fig. 4

Proposed anterior thalamic participation in cognition. Hypothesised mapping of three interleaving, interconnected, ‘cognitive zones’ of anterior thalamic nuclear influence. Each zone maps cognitive functions — spatial processing, attention, and memory to anterior nuclei (as implicated by lesion, recording, anatomical tracing, or other evidence) illustrating their extensive contributions to multiple aspects of cognition. This mapping of functions implies fast-acting, dynamic relations between spatial processing, attentional, and mnemonic processes; spatial processing and attention are deployed during episodic memory encoding and consolidation (as they are contributory processes to memory), but equally they may well be independent of memory during other tasks.