Abstract
Dissection of the neural circuits of the cerebral cortex is essential for studying mechanisms underlying brain function. Herein, combining a retrograde rabies tracing system with fluorescent micro-optical sectional tomography, we investigated long-range input neurons of corticotropin-releasing hormone containing neurons in the six main cortical areas, including the prefrontal, somatosensory, motor, auditory, and visual cortices. The whole brain distribution of input neurons showed similar patterns to input neurons distributed mainly in the adjacent cortical areas, thalamus, and basal forebrain. Reconstruction of continuous three-dimensional datasets showed the anterior and middle thalamus projected mainly to the rostral cortex whereas the posterior and lateral projected to the caudal cortex. In the basal forebrain, immunohistochemical staining showed these cortical areas received afferent information from cholinergic neurons in the substantia innominata and lateral globus pallidus, whereas cholinergic neurons in the diagonal band nucleus projected strongly to the prefrontal and visual cortex. Additionally, dense neurons in the zona incerta and ventral hippocampus were found to project to the prefrontal cortex. These results showed general patterns of cortical input circuits and unique connection patterns of each individual area, allowing for valuable comparisons among the organisation of different cortical areas and new insight into cortical functions.
Highlights
Dissection of the neural circuits of the cerebral cortex is essential for studying mechanisms underlying brain function
The sensory cortex received additional input from the contralateral motor cortex (Fig. 3B). These results show that neurons in the orbitofrontal cortex (OFC) and perirhinal area form wide connections with Corticotropin-releasing hormone (CRH) neurons in diverse cortical areas in both hemispheres and in the anterior cortex received more input from the contralateral cortex than posterior cortical areas (Au and V1)
The central medial thalamic nucleus (CM), centrolateral thalamic nucleus (CL), reuniens thalamic nucleus, and rhomboid thalamic nucleus (Re/Rh) which are near the midline projected to cortical CRH neurons relatively close to the midline, but not to the lateral cortex S2 and auditory cortex (Au). we found that the thalamic nucleus in the peripheral part (AM in anterior; mediodorsal thalamic nucleus (MD) and LD in dorsal; Re/Rh in ventral; medial geniculate nucleus (MG) and dorsal lateral geniculate (DLG) in posterior) connected with CRH neurons in specific cortical areas, while the inner thalamic nucleus had divergent connections with different cortices
Summary
Dissection of the neural circuits of the cerebral cortex is essential for studying mechanisms underlying brain function. By combining the modified rabies virus (RV) tracing system with Cre line m ice[20], recent studies have uncovered the long-range input circuits of CRH neurons in the anterior cingulate cortex (ACC) and have investigated their monosynaptic connections with the cholinergic s ystem[21]. These results are based on two-dimensional sections which lack whole-brain information, especially anatomical information in three-dimensional (3D) space. It is unclear whether input circuits of CRH neurons are similar or if there are some of the same areas in the input circuits that regulate different cortical areas
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