Neurochemical delineation of the supramammillary region of the human hypothalamus

A. MEDINA; D. M. KROLEWSKI; I. A. KERMAN; R. BERNARD; W. BUNNEY; E. G. JONES; H. AKIL; S. J. WATSON
Society for Neuroscience. 2009.

Abstract

The supramammillary area of the hypothalamus is a small but yet very influential diencephalic structure. In rodents, it is considered to exert significant influence over the hippocampus, and it is especially associated with the modulation of theta rhythm, an activity pattern assumed to be important for control of cognitive functions and memory. It is also been suggested that the supramammillary-hippocampal system plays a key role in the development of the hippocampal formation in non human and human primates. However, the availability of human studies is very limited, starting by the definition of its anatomical limits; so far, this is restricted to the assumption of the homology of the area located above the mammillary bodies to that in other mammals. We have previously shown that utilizing mRNAs as anatomical markers combined with neurohistological techniques facilitates the mapping process of the human hypothalamus, bypassing the inherent difficulty associated to the lesser histological differentiation within areas. In this study we use the same approach to look for adequate markers to delineate the supramammillary region of the human hypothalamus. Materials and Methods: Human brain samples were obtained from the Brain Donor Program at the University of California, Irvine. Radioactive in situ hybridization (ISH) was performed on hypothalamic sections from 6 normal subjects using histidine decarboxylase (HDC), GAD 67, calretinin and parvalbumin probes. The sections were afterwards stained using Kluver's protocol. Digitized images of ISH autoradiograms and histological slides were overlaid using Adobe® Photoshop® CS 8.0. One separate hypothalamus block was sectioned at 30 micron thickness to provide a better specimen for Nissl stains and in situ hybridization was also performed in this subject. Results: the supramammillary region in humans can be defined as a calretinin-positive area limited medially by the mammillothalamic/mammillotegmental tract, laterally by the HDC positive neurons from the caudal tuberomammillary complex, and dorsally and ventrally by the parvoalbumin positive cells from the subthalamic and medial mammillary nuclei respectively. Besides calretinin, a few sparse cells in this area expressed HDC and GAD 67.