An Analysis and Representation in an Atlas Reference Space of Putative Appositions from Neurons Expressing Alpha-Melanocyte-Stimulating Hormone with Neurons Expressing Hypocretin/Orexin or Melanin-Concentrating Hormone

The hypothalamus is a brain structure at the center of a variety of regulatory functions that have been explored by scientists and clinicians for almost a century. Among these functions, metabolic regulation and the control of appetitive behaviors have been fields of intensive research. Some of the major neural substrates involved in the hypothalamic control of feeding and the regulation of metabolic state include neuronal populations that express the neuropeptides alpha-melanocyte stimulating hormone (αMSH), melanin-concentrating hormone (MCH) and hypocretin/orexin (H/O). αMSH has been characterized in part as an anorexigenic peptide, while MCH and H/O have been characterized as having orexigenic effects. The functionally opposing nature of these neuropeptides has prompted researchers to investigate the effects that αMSH might have in modulating H/O and MCH actions, which has uncovered structural evidence of putative appositions between axonal fibers from hypothalamic cells expressing αMSH and cell bodies, or somata, of other hypothalamic cells expressing either H/O or MCH. However, these groups did not report their findings within a standardized spatial framework, nor did they provide detailed co-spatial distributions–for the regions of possible synaptic interactions–for these neuropeptides. In the present study, immunohistochemical staining and rigorous atlas-based mapping were used to pinpoint the distributions of αMSH-, MCH- and H/O-immunoreactive somata and fibers throughout the anterior, and tuberal hypothalamus in order to determine regions with a high likelihood of local interactions or co-spatial expression. Additionally, at a finer scale, these methods were employed to report with high-spatial resolution the distributions of possible synaptic interactions of αMSH-ir fibers with either MCH- or H/O-ir somata. Collectively, these data will allow for more quantitative hypothesis-testing to determine whether there is a clear pattern or organization of the distributions of these neuropeptides and their structural interactions