Pathways for Memory, Cognition and Emotional Context: Hippocampal, Subgenual Area 25, and Amygdalar Axons Show Unique Interactions in the Primate Thalamic Reuniens Nucleus

Abstract

The reuniens nucleus (RE) is situated at the most ventral position of the midline thalamus. In rats and mice RE is distinguished by bidirectional connections with the hippocampus and medial prefrontal cortex (mPFC) and a role in memory and cognition. In primates, many foundational questions pertaining to RE remain unresolved. We addressed these issues by investigating the composition of the rhesus monkey RE in both sexes by labeling for GABA, a marker of inhibitory neurons, and for the calcium-binding proteins parvalbumin (PV), calbindin (CB), and calretinin (CR), which label thalamic excitatory neurons that project to cortex. As in rats and mice, the macaque RE was mostly populated by CB and CR neurons, characteristic of matrix-dominant nuclei, and had bidirectional connections with hippocampus and mPFC area 25 (A25). Unlike rodents, we found GABAergic neurons in the monkey RE and a sparser but consistent population of core-associated thalamocortical PV neurons. RE had stronger connections with the basal amygdalar complex than in rats or mice. Amygdalar terminations were enriched with mitochondria and frequently formed successive synapses with the same postsynaptic structures, suggesting an active and robust pathway to RE. Significantly, hippocampal pathways formed multisynaptic complexes that uniquely involved excitatory projection neurons and dendrites of local inhibitory neurons in RE, extending this synaptic principle beyond sensory to high-order thalamic nuclei. Convergent pathways from hippocampus, A25, and amygdala in RE position it to flexibly coordinate activity for memory, cognition, and emotional context, which are disrupted in several psychiatric and neurologic diseases in humans.

Construction of complex memories via parallel distributed cortical–subcortical iterative integration

“… 3 Loops through, e.g. nucleus reuniens are also important [ 120 ] but beyond the scope of this article …”

The inevitable inequality of cortical columns

“…Thalamic PV neurons predominate in nuclei that project to primary cortices. At the other extreme, some other thalamic nuclei, such as the midline, are dominated by CB neurons (e.g., Joyce et al, 2022 ). The midline (limbic) thalamic nuclei project widely to the upper cortical layers in PFC but also to other high-order association cortices.…”

Sleep spindles in primates: modelling the effects of distinct laminar thalamocortical connectivity in core, matrix, and reticular thalamic circuits

“…Importantly, GABAergic local circuit neurons are abundant in all the dorsal thalamic nuclei of primates, and may constitute about 40% of all neurons in the human thalamus (Arcelli et al, 1997; Hunt et al, 1991; Smith et al, 1987), but are not present in all the thalamic nuclei of different mammalian species, and are virtually absent in the thalamus of rodents, with the exception of few first-order thalamic nuclei like the lateral geniculate nucleus (Arcelli et al, 1997; Barbaresi et al, 1986; Gabbott et al, 1986) and the ventral posterior nuclei (Simko and Markram, 2021). The importance of local thalamic inhibition has not been explored in most experimental and computational studies of TC circuits or sleep spindles, with few exceptions (Arcelli et al, 1997; Joyce et al, 2022; Sherman, 2004; Timbie et al, 2020). There is agreement that local inhibition, which is especially abundant in primates, adds complexity to the synaptology and circuitry of the thalamus, in part by facilitating widespread formation of triadic synaptic glomeruli in most thalamic nuclei (Arcelli et al, 1997; Joyce et al, 2022; Sherman, 2004; Timbie et al, 2020), and likely affects the functional properties of TC circuits that can modulate attention, memory consolidation, and spindle tendency.…”

“…The importance of local thalamic inhibition has not been explored in most experimental and computational studies of TC circuits or sleep spindles, with few exceptions (Arcelli et al, 1997; Joyce et al, 2022; Sherman, 2004; Timbie et al, 2020). There is agreement that local inhibition, which is especially abundant in primates, adds complexity to the synaptology and circuitry of the thalamus, in part by facilitating widespread formation of triadic synaptic glomeruli in most thalamic nuclei (Arcelli et al, 1997; Joyce et al, 2022; Sherman, 2004; Timbie et al, 2020), and likely affects the functional properties of TC circuits that can modulate attention, memory consolidation, and spindle tendency.…”