Postmortem anterograde tracing of intrahypothalamic projections of the human dorsomedial nucleus of the hypothalamus

Together with the paraventricular nucleus (PVN), the dorsomedial nucleus of the hypothalamus (DMH) acts as one of the hypothalamic centers that integrate autonomic and central information. The DMH in the rat brain has extensive intrahypothalamic connections and is implicated in a wide variety of functions. Up until now, no knowledge has been available to indicate that the human DMH might have functions similar to those of the rat DMH. In the present study, intrahypothalamic efferent projections of the human DMH were revealed by a recently developed in vitro postmortem tracing method. It was found that the most densely innervated areas are the PVN, the ventromedial nucleus of the hypothalamus, and the area below the PVN. Other significant terminal fields include the periventricular nucleus, the lateral hypothalamic area, and the medial part of the anteroventral hypothalamic area. Scarce fibers project to the suprachiasmatic nucleus, infundibular nucleus, posterior hypothalamic nucleus, and posterior part of the bed nucleus of the stria terminals. The projections of the ventral and dorsal part of the DMH show some differences. The dorsal part of the DMH has denser projections to the dorsal part of the PVN than to the ventral part of the PVN. In contrast, the ventral part of the DMH has denser projections to the ventral part of the PVN. Labeled fibers in the PVN from ventral and dorsal DMH appear to run near many vasopressin and oxytocin neurons of different sizes, and also near some corticotropin‐ releasing hormone neurons, suggesting that the DMH neurons may directly affect the functioning of these PVN neurons. In many aspects, the observed projections of the human DMH resemble those of the rat, indicating that the organization of DMH intrahypothalamic projections of human is similar to that of rat. The functional significance of DMH intrahypothalamic connections is discussed. J. Comp. Neurol. 401:16–33, 1998. © 1998 Wiley‐Liss, Inc.

[1]  L. Bellinger,et al.  The lateral hypothalamic area revisited: Neuroanatomy, body weight regulation, neuroendocrinology and metabolism , 1993, Neuroscience & Biobehavioral Reviews.

[2]  A. Kalsbeek,et al.  Efferent projections of the suprachiasmatic nucleus in the golden hamster (Mesocricetus auratus) , 1993, The Journal of comparative neurology.

[3]  R. Buijs,et al.  Vasopressin fiber pathways in the rat brain following suprachiasmatic nucleus lesioning , 1982, Brain Research.

[4]  J. Dimicco,et al.  Effect of local inhibition of gamma-aminobutyric acid uptake in the dorsomedial hypothalamus on extracellular levels of gamma-aminobutyric acid and on stress-induced tachycardia: a study using microdialysis. , 1990, The Journal of pharmacology and experimental therapeutics.

[5]  W. Cowan,et al.  Direct hypothalamo-autonomic connections , 1976, Brain Research.

[6]  A. Vania Apkarian,et al.  Biotin-dextran: a sensitive anterograde tracer for neuroanatomic studies in rat and monkey , 1992, Journal of Neuroscience Methods.

[7]  M. Steiner,et al.  Neural connections of the suprachiasmatic nucleus and medial hypothalamus of the Syrian hamster (Mesocricetus auratus). , 1994, Journal of anatomy.

[8]  L. P. Morin,et al.  Projections of the suprachiasmatic nuclei, subparaventricular zone and retrochiasmatic area in the golden hamster , 1994, Neuroscience.

[9]  P. Luiten,et al.  Phaseolus vulgaris leuco-agglutinin tracing of intrahypothalamic connections of the lateral, ventromedial, dorsomedial and paraventricular hypothalamic nuclei in the rat , 1987, Brain Research Bulletin.

[10]  M. Markman,et al.  Projections of the suprachiasmatic nucleus to stress‐related areas in the rat hypothalamus: A light and electron microscopic study , 1993, The Journal of comparative neurology.

[11]  J. Pan,et al.  Central nervous system regions involved in the estrogen-induced afternoon prolactin surge. I. Lesion studies. , 1985, Endocrinology.

[12]  P. Sawchenko,et al.  Organization of galanin‐immunoreactive inputs to the paraventricular nucleus with special reference to their relationship to catecholaminergic afferents , 1987, The Journal of comparative neurology.

[13]  W. Cowan,et al.  The efferent connections of the ventromedial nucleus of the hypothalamus of the rat , , 1976, The Journal of comparative neurology.

[14]  S. P. Grossman,et al.  Ingestive behavior in adult rats with dorsomedial hypothalamic lesions , 1981, Physiology & Behavior.

[15]  L. Bellinger,et al.  Effect of ventromedial and dorsomedial hypothalamic lesions on circadian corticosterone rhythms. , 1976, Neuroendocrinology.

[16]  E. Fliers,et al.  The supraoptic and paraventricular nuclei of the human hypothalamus in relation to sex, age and Alzheimer's disease , 1990, Neurobiology of Aging.

[17]  L W Swanson,et al.  Efferent projections of the suprachiasmatic nucleus: II. Studies using retrograde transport of fluorescent dyes and simultaneous peptide immunohistochemistry in the rat , 1987, The Journal of comparative neurology.

[18]  L W Swanson,et al.  Organization of projections from the dorsomedial nucleus of the hypothalamus: A PHA‐L study in the rat , 1996, The Journal of comparative neurology.

[19]  H. Braak,et al.  Anatomy of the human hypothalamus (chiasmatic and tuberal region). , 1992, Progress in brain research.

[20]  R. Ravid,et al.  Localization of corticotropin-releasing hormone (CRH) neurons in the paraventricular nucleus of the human hypothalamus; age-dependent colocalization with vasopressin , 1993, Brain Research.

[21]  A. Matsumoto,et al.  Sex difference in volume of the ventromedial nucleus of the hypothalamus in the rat. , 1983, Endocrinologia japonica.

[22]  W. Kamphorst,et al.  The monoclonal antibody Alz-50, used to reveal cytoskeletal changes in Alzheimer's disease, also reacts with a large subpopulation of somatostatin neurons in the normal human hypothalamus and adjoining areas , 1994, Brain Research.

[23]  R. L. Moss,et al.  Efferent connections of the rat suprachiasmatic nucleus , 1981, Neuroscience.

[24]  L W Swanson,et al.  Hypothalamic integration: organization of the paraventricular and supraoptic nuclei. , 1983, Annual review of neuroscience.

[25]  W. Armstrong,et al.  A biotin-containing compound N-(2-aminoethyl)biotinamide for intracellular labeling and neuronal tracing studies: Comparison with biocytin , 1991, Journal of Neuroscience Methods.

[26]  W. Cowan,et al.  The efferent connections of the suprachiasmatic nucleus of the hypothalamus , 1975, The Journal of comparative neurology.

[27]  L. Bellinger,et al.  The effect of dorsomedial hypothalamic nuclei lesions on body weight regulation , 1979, Neuroscience.

[28]  J. Herman,et al.  Neurocircuitry of stress: central control of the hypothalamo–pituitary–adrenocortical axis , 1997, Trends in Neurosciences.

[29]  L W Swanson,et al.  Efferent projections of the suprachiasmatic nucleus: I. Studies using anterograde transport of Phaseolus vulgaris leucoagglutinin in the rat , 1987, The Journal of comparative neurology.

[30]  P. J. Larsen,et al.  Topographical organization of the rat suprachiasmatic‐paraventriocular projection , 1995, The Journal of comparative neurology.

[31]  S. Schwarzkopf,et al.  Alterations in behavioral responses to stressors following excitotoxin lesions of dorsomedial hypothalamic regions , 1994, Brain Research.

[32]  L. Renaud,et al.  GABA and glutamate mediate rapid neurotransmission from suprachiasmatic nucleus to hypothalamic paraventricular nucleus in rat. , 1996, The Journal of physiology.

[33]  W. Cowan,et al.  An autoradiographic study of the efferent connections of the lateral hypothalamic area in the rat , 1979, The Journal of comparative neurology.

[34]  J. Herman,et al.  Ventral subicular interaction with the hypothalamic paraventricular nucleus: Evidence for a relay in the bed nucleus of the stria terminalis , 1993, The Journal of comparative neurology.

[35]  J. Gunnet,et al.  The interaction of the medial preoptic area and the dorsomedial-ventromedial nuclei of the hypothalamus in the regulation of the mating-induced release of prolactin. , 1985, Neuroendocrinology.

[36]  D. Swaab,et al.  Distribution of vasopressin and vasoactive intestinal polypeptide (VIP) fibers in the human hypothalamus with special emphasis on suprachiasmatic nucleus efferent projections , 1997, The Journal of comparative neurology.

[37]  R. McCusker,et al.  Plasma hormone levels in growth-retarded rats with dorsomedial hypothalamic lesions , 1985, Physiology & Behavior.

[38]  D. Swaab,et al.  Postmortem tracing reveals the organization of hypothalamic projections of the suprachiasmatic nucleus in the human brain , 1998, The Journal of comparative neurology.

[39]  V. Cassone,et al.  Comparative Anatomy of the Mammalian Hypothalamic Suprachiasmatic Nucleus , 1988, Journal of biological rhythms.

[40]  A. Kalsbeek,et al.  GABA receptors in the region of the dorsomedial hypothalamus of rats are implicated in the control of melatonin and corticosterone release. , 1996, Neuroendocrinology.

[41]  A. Reiner,et al.  Biotinylated dextran amine as an anterograde tracer for single- and double-labeling studies , 1992, Journal of Neuroscience Methods.

[42]  A. Kalsbeek,et al.  Peptidergic transmitters of the suprachiasmatic nuclei and the control of circadian rhythmicity. , 1992, Progress in brain research.

[43]  D. Swaab,et al.  Human retinohypothalamic tract as revealed by in vitro postmortem tracing , 1998, The Journal of comparative neurology.

[44]  M. Palkovits,et al.  Norepinephrine and dopamine content of hypothalamic nuclei of the rat. , 1974, Brain research.

[45]  D. Amaral,et al.  The distribution of GABAergic cells, fibers, and terminals in the monkey amygdaloid complex: an immunohistochemical and in situ hybridization study , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[46]  H. Kuypers,et al.  The paraventricular nucleus of the hypothalamus: Cytoarchitectonic subdivisions and organization of projections to the pituitary, dorsal vagal complex, and spinal cord as demonstrated by retrograde fluorescence double‐labeling methods , 1980, The Journal of comparative neurology.

[47]  P. Luiten,et al.  Interrelations between lateral, dorsomedial and ventromedial hypothalamic nuclei in the rat. An HRP study , 1980, Brain Research.

[48]  B. Roland,et al.  Local origins of some GABAergic projections to the paraventricular and supraoptic nuclei of the hypothalamus in the rat , 1993, The Journal of comparative neurology.

[49]  A. Shekhar,et al.  Fear-potentiated startle elevates catecholamine levels in the dorsomedial hypothalamus of rats , 1994, Pharmacology Biochemistry and Behavior.

[50]  J. DiMicco,et al.  Muscimol acts in dorsomedial but not paraventricular hypothalamic nucleus to suppress cardiovascular effects of stress , 1996, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[51]  P. Luiten,et al.  The projections of the dorsomedial hypothalamic nucleus in the rat , 1986, Brain Research Bulletin.

[52]  K. Kitahama,et al.  Neurons containing messenger RNA encoding glutamate decarboxylase in rat hypothalamus demonstrated by in situ hybridization, with special emphasis on cell groups in medial preoptic area, anterior hypothalamic area and dorsomedial hypothalamic nucleus , 1990, Neuroscience.

[53]  L. Bernardis Hypophagia, hypodipsia and hypoactivity following dorsomedial hypothalamic lesions. , 1972, Physiology & behavior.

[54]  J. Tasker,et al.  Physiological Mapping of Local Inhibitory Inputs to the Hypothalamic Paraventricular Nucleus , 1996, The Journal of Neuroscience.

[55]  P. Luiten,et al.  The course of paraventricular hypothalamic efferents to autonomic structures in medulla and spinal cord , 1985, Brain Research.

[56]  F E Bloom,et al.  Central catecholamine neuron systems: anatomy and physiology of the norepinephrine and epinephrine systems. , 1979, Annual review of neuroscience.