Bifurcating Neurons In The Anterior Thalamic Nuclei

Abstract

The anterior thalamic nuclei (ATN) form a nodal point within a hippocampal-cingulate-diencephalic memory system. ATN projections to different brain structures are conventionally viewed as distinct, but ATN neurons may send collaterals to multiple structures. The anteromedial subregion (AM) is the primary source of efferents to the medial prefrontal cortex (mPFC). Using a dual-retrograde neurotracer strategy, we discovered bifurcating AM neurons for tracers placed in the mPFC when paired with other regions. A semi-quantitative analysis found a high proportion of AM neurons (~36%) showed collateral projections when the mPFC was paired with dorsal subiculum (dSub); 20% were evident for mPFC paired with caudal retrosplenial cortex (cRSC); and 6% was found for mPFC and ventral hippocampal formation (vHF). About 10% of bifurcating AM neurons was also identified when the mPFC was not included, that is, for cRSC with dSub, and cRSC with vHF. Similar percentages of bifurcating neurons were also found within the anterior region of the adjacent nucleus reuniens (Re). The high frequency of bifurcating neurons suggests a new perspective for ATN function. These neurons would facilitate direct coordination among distal neural ensembles to support episodic memory and may explain why the ATN is a critical region for diencephalic amnesia.

Collateral rostral thalamic projections to prelimbic, infralimbic, anterior cingulate and retrosplenial cortices in the rat brain

“…Finding an appreciable proportion of neurons in nucleus reuniens that project to both medial prefrontal cortex and the hippocampal formation ($36%) appears inconsistent with the 5%-10% previously reported for the same termination pairings (Hoover & Vertes, 2012;Varela et al, 2014). Furthermore, it had been observed that considerably more double-labelled cells are present in the ventral hippocampal formation (Hoover & Vertes, 2012), something not described in the later study (Pei et al, 2021). In addition, Pei et al (2021) reported appreciable populations of double-labelled cells in both the anteromedial nucleus ($20%) and nucleus reuniens (26%) for the medial prefrontal cortex/retrosplenial cortex pairing (Pei et al, 2021), yet this same combination gave proportions closer to zero in the present study.…”

“…A largely complementary study also investigated collateral cortical projections from the anteromedial nucleus and nucleus reuniens (Pei et al, 2021). Much of their focus was on whether cortical collaterals reach the hippocampal formation (Pei et al, 2021).…”

“…A largely complementary study also investigated collateral cortical projections from the anteromedial nucleus and nucleus reuniens (Pei et al, 2021). Much of their focus was on whether cortical collaterals reach the hippocampal formation (Pei et al, 2021). Consequently, the study included medial prefrontal cortex/dorsal subiculum, medial prefrontal cortex/ventral subiculum, caudal retrosplenial/dorsal subiculum and caudal retrosplenial/ ventral subiculum injection pairings.…”

“…(Until both target areas are filled with tracer, the resulting double-cell counts will always be an underestimate.) One unintended consequence, however, was that 'medial prefrontal' cortex injections extended into anterior cingulate cortex (Pei et al, 2021), a factor that might increase the proportions of double-labelled cells within the anteromedial nucleus and nucleus reuniens (see anterior cingulate/ retrosplenial pairs here and Horikawa et al, 1988). Furthermore, their cell counts (Pei et al, 2021) just involved a restricted subarea of each target nucleus.…”

“…A related investigation (Condé et al, 1990), which looked for inputs to the anterior cingulate cortex and other medial prefrontal areas, described how midline thalamic sites, such as nucleus reuniens contain modest numbers of bifurcating neurons. A more recent study (Pei et al, 2021) extended the termination areas under investigation by including the hippocampal formation but just focussed on projections from the anteromedial nucleus and nucleus reuniens. That study reported appreciably higher proportions of double-labelled neurons that collaterise to terminate in multiple areas.…”