Anatomy and connectivity of the Göttingen minipig subgenual cortex (Brodmann area 25 homologue).

Background: The subgenual gyrus is a promising target for deep brain stimulation (DBS) against depression. However, to optimize this treatment modality, we need translational animal models.

Aim: To describe the anatomy and connectivity of the Göttingen minipig subgenual area (sgC).

Materials and methods: The frontal pole of 5 minipigs was cryosectioned into 40 μm coronal and horizontal sections and stained with Nissl and NeuN-immunohistochemistry to visualize cytoarchitecture and cortical lamination. Eight animals were unilaterally stereotaxically injected in the sgC with anterograde (BDA) and retrograde (FluoroGold) tracers to reveal the sgC connectivity.

Results: In homology with human nomenclature (Brodmann 1909), the minipig sgC can be subdivided into three distinct areas named area 25 (BA25), area 33 (BA33), and indusium griseum (IG). BA25 is a thin agranular cortex, approximately 1 mm thick. Characteristically, perpendicular to the pial surface, cell-poor cortical columns separate the otherwise cell-rich cortex of layer II, III and V. In layer V the cells are of similar size as seen in layer III, while layer VI contains more widely dispersed neurons. BA33 is less differentiated than BA25. Accordingly, the cortex is thinner and displays a complete lack of laminar differentiation due to diffusely arranged small, lightly stained neurons. It abuts the IG, which is a neuron-dense band of heavily stained small neurons separating BA33 directly from the corpus callosum and the posteriorly located septal nuclear area. Due to the limited area size and nearby location to the lateral ventricle and longitudinal cerebral fissure, only 3/8 animals received sgC injections with an antero- and retrograde tracer mixture. Retrograde tracing was seen primarily to the neighbouring ipsilateral ventral- and mPFC areas with some contralateral labelling as well. Prominent projections were furthermore observed from the ipsilateral insula, the medial aspect of the amygdala and the hippocampal formation, diencephalon and the brainstem ventral tegmental area. Anterograde tracing revealed prominent projections to the neighbouring medial prefrontal, mPFC and cingulate cortex, while moderate staining was noted in the hippocampus and adjoining piriform cortex.

Conclusion: The minipig sgC displays a cytoarchitectonic pattern and connectivity like the human and may be well suited for further translational studies on BA25-DBS against depression.