Individual mediodorsal thalamic neurons project to multiple areas of the rat prefrontal cortex: A single neuron‐tracing study using virus vectors

Abstract

The prefrontal cortex has an important role in a variety of cognitive and executive processes, and is generally defined by its reciprocal connections with the mediodorsal thalamic nucleus (MD). The rat MD is mainly subdivided into three segments, the medial (MDm), central (MDc), and lateral (MDl) divisions, on the basis of the cytoarchitecture and chemoarchitecture. The MD segments are known to topographically project to multiple prefrontal areas at the population level: the MDm mainly to the prelimbic, infralimbic, and agranular insular areas; the MDc to the orbital and agranular insular areas; and the MDl to the prelimbic and anterior cingulate areas. However, it is unknown whether individual MD neurons project to single or multiple prefrontal cortical areas. In the present study, we visualized individual MD neurons with Sindbis virus vectors, and reconstructed whole structures of MD neurons. While the main cortical projection targets of MDm, MDc, and MDl neurons were generally consistent with those of previous results, it was found that individual MD neurons sent their axon fibers to multiple prefrontal areas, and displayed various projection patterns in the target areas. Furthermore, the axons of single MD neurons were not homogeneously spread, but were rather distributed to form patchy axon arbors approximately 1 mm in diameter. The multiple-area projections and patchy axon arbors of single MD neurons might be able to coactivate cortical neuron groups in distant prefrontal areas simultaneously. Furthermore, considerable heterogeneity of the projection patterns is likely, to recruit the different sets of cortical neurons, and thus contributes to a variety of prefrontal functions. J. Comp. Neurol. 525:166-185, 2017. © 2016 Wiley Periodicals, Inc.

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

“…Recently, single‐cell tracing studies of the above three higher‐order thalamic regions demonstrated that single neurons of these thalamic regions formed multiple axon arbors in the different cortical areas (Ohno et al, ; Nakamura et al, ; Kuramoto et al, ). Accordingly, the formation of multiple axon arbors may be common characteristics as higher‐order thalamic nuclei neurons.…”

“…Thus, the corticothalamic excitatory input may function as a driver input for the ventral Sm. Similarly, several thalamic regions, such as the anterior region of the posterior nuclei, the lateral subdivision of the lateral posterior nucleus, and mediodorsal nucleus, have been reported to show few or very weak VGluT2 immunoreactivity (Kaneko, Fujiyama, & Hioki, ; Ohno et al, ; Nakamura, Hioki, Furuta, & Kaneko, ; Kuramoto et al, ). These three thalamic regions have been considered to be higher‐order thalamic nuclei (Varela, ), and suggested to receive driver inputs from layer 5 of the cerebral cortex (Groenewegen, ; Bourassa & Deschênes, ; Veinante, Laballée, & Deschênes, ).…”

Secondary Motor Cortex: Where ‘Sensory’ Meets ‘Motor’ in the Rodent Frontal Cortex

“…Rose and Woolsey originally proposed the terminal fields of projections from the mediodorsal nucleus of the thalamus as a criterion for defining the prefrontal cortex [82]. Axons from the lateral division of MD thalamus project to M2 [19,83,84]. On the whole, MD thalamic projections can be found in M2 as well as orbital, prelimbic, infralimbic, anterior cingulate, and agranular insular regions, but they are absent in primary motor and sensory cortices in mice [85].…”

Thalamic control of functional cortical connectivity

“…Anatomically, thalamic output to the cortex is quite variable, with only a minority of thalamic circuits exhibiting a topographic and spatially restricted innervation of a single cortical target [30,31]. Additionally, many thalamic circuits receive convergent inputs from a single or multiple cortical regions that do not appear to be compatible with the idea of topographic relay [32].…”