Research reportThe posterior hypothalamic area: chemoarchitecture and afferent connections
Introduction
The posterior hypothalamic area (PHA) is the most caudal of the medial zone hypothalamic cell populations. Ablation studies, electrical and chemical stimulation, and electrophysiological recordings suggest that the PHA is involved in the control of sleep–wake cycles [59], [74], [117], the modulation of brainstem generated hippocampal θ rhythms [7], [120], cardiovascular regulation [9], [66], [108], [125] and the expression of defensive–aggressive behavior [103], [126]. Involvement in such a diverse range of functions would require that the PHA be a major site of integration. Recent observations implicating a subset of PHA neurons which produce hypocretin [57], [93] in the pathophysiology of the sleep disorder, narcolepsy [75], [82], emphasize the importance of understanding the connections of this region of the hypothalamus. Although its efferent projections have been studied in detail [119], [121] the sources of afferents to the PHA have not been presented in a comprehensive report.
In the present study, we use the retrograde tracers Fluorogold (FG) and PRV to define the origin of afferents to the PHA. In addition, the cytoarchitecture and chemoarchitecture of the PHA is examined to better define the area’s borders, and the neurochemical identity of its component structures. Finally, we exploit the ability of PRV to pass transynaptically through neuronal circuits to elucidate neuronal networks providing input to the PHA.
Section snippets
Animals
Forty-five male Sprague–Dawley rats (300–350 g) were housed in clear plastic cages in 12:12-h light–dark cycles (lights on at 07:00 h) with free access to Purina rat chow and water.
Surgery
All surgical procedures were carried out with the animals under deep, general anesthesia produced by intraperitoneal injections of 80 mg ketamine and 20 mg xylazine (Sigma, St. Louis, MO) per kg body weight. The Institutional Animal Care and Use Committee of the University of Pittsburgh approved all procedures
Cytoarchitecture
The PHA contains a homogeneous population of small to medium sized cells, with occasional large, darkly staining neurons scattered throughout the rostrocaudal extent of the nucleus. Cell packing density is low relative to neighboring hypothalamic structures, and fiber tracks course through and around the PHA along its rostrocaudal extent (Fig. 1). Major fiber tracks and cell morphology and packing density differences of adjacent structures demarcate the boundaries of the area dorsally
Neuronal organization of the PHA
Our analysis of PHA cytoarchitecture confirms and extends that of previous studies [36], [118], [121]. In particular, we have extended the definition of the anterior portion of the PHA to include the region of the dorsal hypothalamus caudal to the dorsal hypothalamic nucleus.
The PHA contains the caudal portion of three groups of peptide-containing neurons. NPY+ neurons appear to produce intrinsic hypothalamic projections, whereas the MCH and HCT populations have widespread projections,
Acknowledgements
Supported by NIH Grant NS-16304. We are grateful to Drs. J. Patrick Card and Lynn Enquist for providing supplies of PRV and PRV antiserum, to Dr. Anthony van den Pol for providing HCT antiserum and to Dr. Paul Sawchenko for providing MCH antiserum.
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