The neuroanatomy and connectivity of the ventral striatum and ventral capsule area in the Göttingen minipig.

A considerable proportion of patients with major depressive disorder (MDD) do not respond to current treatments. Deep brain stimulation has shown promise as an intervention but has yielded inconsistent outcomes, potentially due to the complex biopsychosocial nature of MDD and the lack of standardized large animal models. The ventral striatum/ventral capsule brain area (VS/VC), involved in emotional and behavioral regulation, is a proposed DBS target. The Göttingen minipig (GM) is an emerging non-primate large animal model; however, the anatomy and connectivity of the GM VS/VC remain poorly characterized. To characterize the neuroanatomy and connectivity of the GM VS/VC region, we have used four female minipigs, which underwent MRI-guided stereotaxic unilateral injection of retrograde (FluoroGold) and anterograde (Biotinylated Dextran Amine) tracers into the VS/VC. Postmortem brains were coronally cryosectioned into 40 µm-thick sections, Nissl-stained, and analyzed for tracer distribution. Additional non-injected GM brains were immunostained using antibodies against calbindin, substance P, myelin basic protein, DARPP-32, tyrosine hydroxylase, and choline acetyltransferase to describe cytoarchitecture. The GM VS/VC exhibited bidirectional connectivity with limbic, associative, and sensorimotor regions, paralleling human nigrostriatal and mesolimbic circuits. The cytoarchitecture, particularly of the nucleus accumbens, is similar to that of primates, including the human brain. The GM VS/VC demonstrates anatomical and connectivity features similar to those found in humans and rodents, supporting its translational potential for modeling neuropsychiatric conditions and testing interventions such as DBS.