Identifying the Functional Architecture of the Human Ventral Tegmental Area and the Substantia Nigra using High Resolution Magnetic Resonance Imaging

32 | MAY 2009 | VOLUME 1 VANDERBILT REVIEWS | NEUROSCIENCE ©2009 Vanderbilt Brain Institute. All rights reserved. ANATOMY OF THE VTA AND SNc The anatomy of the VTA and SNc is unique and challenging to study because of its location in the brain, cellular profile and complex interconnections. Nonetheless, an overview of the anatomy is essential to localize the source of an MRI signal, optimize the parameters required to image this part of the brain and correlate it with brain function. The VTA and SNc are located in the ventral portion of the midbrain brain stem area, and they both vary in size and cytoarchitecture. The VTA is approximately 60mm in size and consists of heterogeneous groups of neurons that are part of the A10 dopaminergic system. The SNc is approximately 1100mm in size and is part of the A9 dopaminergic system. A10 DA fibers contained within the ventromedial midbrain, consist of small diameter (15-30μm), non-myelinated axons that ascend in the medial forebrain bundle (MFB). The A9 DA fibers, on the other hand, vary in size (2040μm) and extend from the medial lemniscus to the lateral border of the cerebral peduncles. The VTA is further subdivided into separate nuclei based on their location and cellular profile, and the neuronal populations in these subdivisions tend to be mediolaterally arranged. The SN is topographically divided into two subdivisions, the pars compacta and pars reticulata. The compacta cells (SNc) have larger cell bodies, thicker and longer dendrites, more numerous dendritic segments and denser neuromelanin granules compared to the reticulata cells. The DA neurons in the VTA have widespread reciprocal connections with sub-cortical and cortical areas of the brain, making this region a major site of information integration. It has reciprocal connections with limbic cortices through the mesolimbic pathway, including the nucleus accumbens (NAc), amygdala, cingulate cortex, and the hippocampal complex. It has efferent and afferent associations with the prefrontal cortex, insular cortex, some sensory, motor and association areas (the mesocortical pathway), and with various nuclei of the thalamus and hypothalamus. It is also reciprocally connected to the dorsal raphe nuclei, locus ceruleus, various brain stem nuclei, the superior colliculus, reticular formation periaqueductal gray, and the spinal cord. Mesocortical projections tend to have their origin dorsorostrally in the VTA, and the mesolimbic projections originate in the ventrocaudal Identifying the Functional Architecture of the Human Ventral Tegmental Area and the Substantia Nigra using High Resolution Magnetic Resonance Imaging