Elsevier

Brain Research

Volume 889, Issues 1–2, 19 January 2001, Pages 1-22
Brain Research

Research report
The posterior hypothalamic area: chemoarchitecture and afferent connections

https://doi.org/10.1016/S0006-8993(00)03015-8Get rights and content

Abstract

This study provides an analysis of the chemoarchitecture of the posterior hypothalamic area (PHA) and a retrograde transport analysis of inputs to the PHA in the rat. The chemoarchitectural analysis reveals that the majority of PHA neurons contain glutamate. Hypocretin, melanin concentrating hormone, tyrosine hydroxylase, neuropeptide Y and γ-aminobutyric acid are also found in subsets of PHA neurons, and fibers immunoreactive for these substances as well as for serotonin, dopamine-β-hydroxylase and met-enkephalin are observed in the area and aid in the delineation of its borders. The retrograde tracing study demonstrates that the PHA receives input from multiple, diverse neuron populations. Descending projections to the PHA arise from the limbic forebrain (cingulate cortex and lateral septum) and both the medial and lateral hypothalamus. Subcortical visual nuclei, including the ventral lateral geniculate nucleus and intergeniculate leaflet, pretectal area, and superior colliculus, and the subthalamus (zona incerta, fields of Forel) also project to the PHA. Ascending projections to the PHA arise from brainstem cholinergic nuclei, the reticular formation, midbrain raphe nuclei, periaqueductal gray and parabrachial nucleus. Retrograde transport studies using the psuedorabies virus (PRV) demonstrate that the PHA receives input indirectly from the hippocampus, amygdala and suprachiasmatic nucleus through circuits including nuclei in the limbic forebrain and hypothalamus. These data suggest that the PHA is important in the neural control of behavioral state, modulating aspects of hippocampal, autonomic and cortical function as they relate to the elaboration of adaptive behavior.

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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