Abstract
Nucleus accumbens (NAcc) has been implicated in several psychiatric disorders such as treatment resistant depression (TRD), and obsessive-compulsive disorder (OCD), and has been an ongoing experimental target for deep brain stimulation (DBS) in both rats and humans. In order to translate basic scientific results from rodents to the human setting a large animal model is needed to thoroughly study the effect of such therapeutic interventions. The aim of the study was, accordingly, to describe the basic anatomy of the Göttingen minipig NAcc and its retrograde connections. Tracing was carried out by MRI-guided stereotactic unilateral fluorogold injections in the NAcc of Göttingen minipigs. After 2 weeks the brains were sectioned and subsequently stained with Nissl-, autometallographic (AMG) development of myelin, and DARPP-32 and calbindin immunohistochemistry. The minipig NAcc was divided in a central core and an outer medial, ventral and lateral shell. We confirmed the NAcc to be a large and well-segregated structure toward its medial, ventral and lateral borders. The fluorogold tracing revealed inputs to NAcc from the medial parts of the prefrontal cortex, BA 25 (subgenual cortex), insula bilaterally, amygdala, the CA1-region of hippocampus, entorhinal cortex, subiculum, paraventricular and anterior parts of thalamus, dorsomedial parts of hypothalamus, substantia nigra, ventral tegmental area (VTA), the retrorubral field and the dorsal and median raphe nuclei. In conclusion the Göttingen minipig NAcc is a large ventral striatal structure that can be divided into a core and shell with prominent afferent connections from several subrhinal and infra-/prelimbic brain areas.
Highlights
Nucleus accumbens (NAcc) has been implicated in several psychiatric disorders such as depression and obsessive compulsive disorder (OCD) and has been an ongoing experimental target for deep brain stimulation (DBS) in rats, primates and humans (Schlaepfer et al, 2007; Bewernick et al, 2010; de Koning et al, 2011; Li et al, 2013).In humans NAcc forms the main part of the so-called ventral striatum located beneath the anterior limb of the internal capsule where the head of the caudate nucleus and the ventroanterior part of putamen meet (Lucas-Neto et al, 2013)
All experimental protocols were approved by the Danish Council of Animal Research Ethics (DANCARE). 6 Göttingen minipigs were used in the basic anatomy study of NAcc and 5 other animals successfully received an MRI-guided injection of 1 μL FluoroGold (FG a selectively fluorescent retrograde tracer, hydroxyl-stilbamidin methanesulfonate from Fluorochrome, Denver, CO; CAT no H22845, Molecular Probes Inc. diluted to 2% in distilled water) on one side of the brain in the tracing part
DARPP-32 is first and foremost localized to regions that receive dopaminergic innervation and the highest DARPP-32 levels are found in caudatoputamen, NAcc, olfactory tubercle, bed nucleus of stria terminalis, and portions of the amygdaloid complex with DARPP-32 immunoreactivity being present in neuronal cell bodies and dendrites (Hemmings et al, 1984; Svenningsson et al, 2004)
Summary
In humans NAcc forms the main part of the so-called ventral striatum located beneath the anterior limb of the internal capsule where the head of the caudate nucleus and the ventroanterior part of putamen meet (Lucas-Neto et al, 2013). The dorsal and lateral borders of NAcc to the rest of striatum are, more difficult to define. Cytoarchitecture and immunohistochemical characteristics indicate that no sharp borders between NAcc and the rest of the striatum exist (Voorn et al, 2004) and the NAcc blends in with the rest of the striatum in Nissl stained sections (Heimer et al, 1997). NAcc was initially divided into two regions—an outer medial, ventral, and lateral shell and a more dorsal and centrally located core based on differences in cytology and chemoarchitectonics as well as a differential distribution of cholecystokininimmunoreactivity (Záborszky et al, 1985). Today calbindin immunohistochemistry is generally considered the most accepted staining for making this distinction (Meredith et al, 1996; Heimer et al, 1997; Groenewegen et al, 1999; Brauer et al, 2000)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
