A Direct Comparison of Afferents to the Rat Anterior Thalamic Nuclei and Nucleus Reuniens: Overlapping But Different

Abstract

Both nucleus reuniens and the anterior thalamic nuclei are densely interconnected with medial cortical and hippocampal areas, connections that reflect their respective contributions to learning and memory. To better appreciate their comparative roles, pairs of different retrograde tracers were placed in these two thalamic sites in adult rats. Both thalamic sites receive modest cortical inputs from layer V that contrasted with much denser projections from layer VI. Despite frequent overlap in layer VI, ventral prefrontal and anterior cingulate inputs to nucleus reuniens were concentrated in the deepest sublayer (VIb). Meanwhile, inputs to the anterior thalamic nuclei originated more evenly from both sublayers VIa and VIb, with the result that they were often located more superficially than the projections to nucleus reuniens. Again, while the many hippocampal (subiculum) neurons projecting to nucleus reuniens and the anterior thalamic nuclei were partially intermingled within the deep cellular parts of the subiculum, cells projecting to nucleus reuniens consistently tended to lie even deeper, i.e., immediately adjacent to the alveus.Variable numbers of double-labelled cells were present in those cortical and subicular portions where the two cell populations intermingled, though they remained in a minority. Our data also show how projections to these two thalamic sites are organized in opposing dorsal/ventral and rostral/caudal gradients across both the cortex and hippocampal formation. While the anterior thalamic nuclei are preferentially innervated by dorsal cortical sites, more ventral frontal sites preferentially reach nucleus reuniens. These anatomical differences may underpin the complementary cognitive functions of these two thalamic areas. Significance statementBoth nucleus reuniens and the anterior thalamic nuclei link frontal cortical areas with the hippocampal formation. We show that the cortical and hippocampal projections to these thalamic sites show intermingled but opposing gradients of origin across the cerebral cortex (anterior thalamic -more dorsal, nucleus reuniens -more ventral), with their respective afferents typically arising from different neurons. There is also a repeated tendency across cortical areas for nucleus reuniens inputs to arise from the very deepest layer (VIb), while anterior thalamic inputs are often slightly more superficial, located across VIb and VIa. A similar depth distinction is again seen in the subiculum. These patterns indicate a separation of information reaching these two thalamic sites, alongside functional divisions within cortical layer VI. Case # CTB injection site FB injection site mPFC layer VI: Main distribution of retrogradely labelled cells mPFC layer V: (typically much fewer cells than VI) Distribution of retrogradely labelled cells in the subiculum #1

The anterior thalamic nuclei: core components of a tripartite episodic memory system

“…Furthermore, although the anterior thalamic nuclei and nucleus reuniens appear to be connected to overlapping cortical sites, the respective inputs from these regions are largely separated by topography and lamina 62 , indicative of complementary functions. This difference can be seen in their respective importance for linking prefrontal (reuniens) and cingulate/retrosplenial regions (anterior thalamic nuclei) to the hippocampus 62,78 . In association with its prefrontal connections, the rodent nucleus reuniens assists spatial working memory 79 , gating information to the hippocampus 80 .…”

“…The anterior thalamic nuclei stand out among medial diencephalic structures as they receive dense, direct hippocampal and parahippocampal projections (Fig. 2 ; Table 1) from the subiculum, presubiculum, and postsubiculum, as well as providing direct return projections to the same sites [60][61][62][63] . Importantly, comparable sets of connections are present in rodents and nonhuman primates 64 .…”

“…Although nucleus reuniens is also reciprocally connected with the hippocampus, including direct inputs to CA1, it only receives sparse inputs from the mammillary bodies 76,77 and retrosplenial cortex 62 in rats. Furthermore, although the anterior thalamic nuclei and nucleus reuniens appear to be connected to overlapping cortical sites, the respective inputs from these regions are largely separated by topography and lamina 62 , indicative of complementary functions. This difference can be seen in their respective importance for linking prefrontal (reuniens) and cingulate/retrosplenial regions (anterior thalamic nuclei) to the hippocampus 62,78 .…”

“…Sites such as the prelimbic, anterior cingulate, and retrosplenial cortices project to the anterior thalamic nuclei, but largely fail to directly innervate the hippocampal formation 64, ; trans-synaptic tracing in rats further confirms that the anterior thalamic nuclei form a major monosynaptic route from these cortical regions to the dorsal hippocampal formation 78 . Consequently, along with the nucleus reuniens 62,78 , the anterior thalamic nuclei provide a potentially important (but rarely recognised) subcortical route, allowing frontal sites to influence hippocampal activity.…”

Hearing Loss Increases Inhibitory Effects of Prefrontal Cortex Stimulation on Sound Evoked Activity in Medial Geniculate Nucleus

“…Another critical component of sensory gating circuitry is the thalamus, the obligatory relay en route to cortex for all sensory input, but olfactory (Saalmann et al, 2012;Halassa and Kastner, 2017). In agreement, multiple pathways from PFC to thalamus have been shown to exist (Mathiasen et al, 2021;Rios-Florez et al, 2021).…”