Dorsal and ventral parts of thalamic nucleus submedius project to different areas of rat orbitofrontal cortex: A single neuron‐tracing study using virus vectors

Abstract

The rodent orbitofrontal cortex is involved in a variety of cognitive and behavioral functions that require thalamic input to be successfully expressed. Although the thalamic nucleus submedius (Sm) is a major source of afferents to the orbitofrontal cortex, thalamocortical projection from the Sm has not been fully elucidated. In the present study, we first divided the rat Sm into dorsal and ventral parts according to the distribution of vesicular glutamate transporter 2-immunoreactive varicosities, which were somatosensory afferents from the brain stem. Subsequently we investigated dendritic and axonal arborizations of individual dorsal and ventral Sm neurons by visualizing the processes with Sindbis virus vectors expressing membrane-targeted fluorescent proteins. The number of dendritic processes of ventral Sm neurons was greater than that of dorsal Sm neurons. In the cerebral cortex, all the reconstructed Sm neurons sent axons primarily to layers 2-5. Interestingly, dorsal Sm neurons formed a single axon arbor exclusively within the ventrolateral orbital area, whereas ventral Sm neurons made two axon arbors in the lateral orbital and ventral orbital areas simultaneously. The spread of each axon arbor was 500-1000 µm in diameter in the direction tangential to the cortical surface. These results indicate that the dorsal and ventral Sm comprise two distinct thalamocortical pathways. The dorsal Sm pathway relay somatosensory information to the ventrolateral orbital area and may be involved in emotional and aversive aspects of nociceptive information processing, whereas the ventral Sm pathway seems to co-activate distant orbitofrontal cortical areas, and may link their functions under certain circumstances.

Organisation of afferents along the anterior-posterior and medial-lateral axes of the rat orbitofrontal cortex

“…Our results revealed that PVO receives most Sub projections from the most anterior half of the Sub, especially from the dorsal portion, and slightly less from the ventral part. Intriguingly, results from previous tracing studies (Kuramoto et al, 2017;Reep et al, 1996) revealed that the anterior portion of the ventral OFC receives inputs from SubV, suggesting a potential anteriorposterior distinction might also be present within ventral OFC.…”

“…However, we also identified a novel pattern of Sub anterior-posterior projections which provides the clearest evidence of a distinction in afferents across the three OFC subregions we investigated in our study: ALO, PLO and PVO. In addition to these OFC subdivisions already mentioned, Sub also sends projections to MO (Kuramoto et al, 2017;Yoshida et al, 1992). Most of the double-or triplelabelled cells we observed were present in the Sub and it has previously reported there are neurons in this region that simultaneously project to lateral and ventral OFC, potentially linking their functions under certain conditions (Kuramoto et al, 2017).…”

“…In addition to these OFC subdivisions already mentioned, Sub also sends projections to MO (Kuramoto et al, 2017;Yoshida et al, 1992). Most of the double-or triplelabelled cells we observed were present in the Sub and it has previously reported there are neurons in this region that simultaneously project to lateral and ventral OFC, potentially linking their functions under certain conditions (Kuramoto et al, 2017). While little is known about the function of this thalamic nucleus, recent studies have explored the functional significance of its connectivity with the OFC, revealing that an intact Sub is necessary for updating both stimulus-outcome (Alcaraz et al, 2015) and action-outcome associations (Fresno, Parkes, Faugère, Coutureau, & Wolff, 2019).…”

“…The submedius nucleus of the thalamus shares strong reciprocal connections with the OFC, especially with VO/LO (Alcaraz et al, 2015;Coffield, Bowen, & Miletic, 1992;Kuramoto et al, 2017;Reep, Corwin, & King, 1996;Yoshida, Dostrovsky, & Chiang, 1992). In our tracing study, the most pronounced labelling in the brain of all subjects was seen in this area, with all portions of this thalamic nucleus projecting to every region of the OFC that we investigated (Figures 6, 7).…”

Layer-specific serotonergic induction of long-term depression in the prefrontal cortex of rats

“…In the OFC, the feedforward inputs from other cortex and inputs from the amygdala terminate preferentially onto L2/3 while nonspecific thalamic relay nucleus and higher order cortex projects mainly onto L1 in rats [ 17 - 19 ] and macaque monkeys [ 20 ]. Especially, the thalamic nucleus submedius projects primarily to layers 2/3/5 of the OFC in mice [ 21 ]. The PFC also receives dense serotonergic innervation from dorsal and medial raphe nuclei and cholinergic innervation from the basal forebrain and basal ganglia [ 22 , 23 ].…”