Anatomy of the Opioid-Systems of the Brain Karl M
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The Role of the Hypothalamic Dorsomedial Nucleus in the Central Regulation of Food Intake
The role of the hypothalamic dorsomedial nucleus in the central regulation of food intake Ph.D. thesis Éva Dobolyiné Renner Semmelweis University Szentágothai János Neuroscience Doctoral School Ph.D. Supervisor: Prof. Miklós Palkovits, member of the HAS Opponents: Prof. Dr. Halasy Katalin, Ph.D., D.Sci. Dr. Oláh Márk, M.D., Ph.D. Examination board: Prof. Dr. Vígh Béla, M.D., Ph.D., D.Sci Dr. Kovács Krisztina Judit, Ph.D., D.Sci. Dr. Lovas Gábor, M.D., Ph.D. Budapest 2013 1. Introduction The central role of the hypothalamus in the regulation of food intake and energy expenditure has long been established. The hypothalamus receives hormonal input such as insulin, leptin, and ghrelin from the periphery. The gate for the most important adiposity signals is the arcuate nucleus, which contains neurons expressing orexigenic and anorexigenic peptides, respectively. These neurons convey peripheral input to the paraventricular and ventromedial nuclei, and the lateral hypothalamic area, which all play critical roles in body weight regulations. The hypothalamic dorsomedial nucleus (DMH) has also been implicated in the regulation of body weight homeostasis along with other hypothalamic nuclei including the arcuate, ventromedial, and paraventricular nuclei as well as the lateral hypothalamus. Lesions of the DMH affected ingestive behavior. Electrophysiological data suggested that neurons in this nucleus integrate hormonal input and ascending brainstem information and, in turn, modulate food intake and energy balance. In response to refeeding of fasted rats, Fos-activated neurons were reported in the DMH. Major projections relay vagus-mediated signals from the gastrointestinal tract, and humoral signals to the hypothalamus from the nucleus of the solitary tract (NTS), a viscerosensory cell group in the dorsomedial medulla. -
Resting State Connectivity of the Human Habenula at Ultra-High Field
Author’s Accepted Manuscript Resting State Connectivity of the Human Habenula at Ultra-High Field Salvatore Torrisi, Camilla L. Nord, Nicholas L. Balderston, Jonathan P. Roiser, Christian Grillon, Monique Ernst www.elsevier.com PII: S1053-8119(16)30587-0 DOI: http://dx.doi.org/10.1016/j.neuroimage.2016.10.034 Reference: YNIMG13531 To appear in: NeuroImage Received date: 26 August 2016 Accepted date: 20 October 2016 Cite this article as: Salvatore Torrisi, Camilla L. Nord, Nicholas L. Balderston, Jonathan P. Roiser, Christian Grillon and Monique Ernst, Resting State Connectivity of the Human Habenula at Ultra-High Field, NeuroImage, http://dx.doi.org/10.1016/j.neuroimage.2016.10.034 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. 1 Resting State Connectivity of the Human Habenula at Ultra-High Field Salvatore Torrisi1, Camilla L. Nord2, Nicholas L. Balderston1, Jonathan P. Roiser2, Christian Grillon1, Monique Ernst1 Affiliations 1 Section on the Neurobiology of Fear and Anxiety, National Institute of Mental Health, Bethesda, MD 2 Neuroscience and Cognitive Neuropsychiatry group, University of College, London, UK Abstract The habenula, a portion of the epithalamus, is implicated in the pathophysiology of depression, anxiety and addiction disorders. -
Visual and Electrosensory Circuits of the Diencephalon in Mormyrids: an Evolutionary Perspective
THE JOURNAL OF COMPARATIVE NEUROLOGY 297:537-552 (1990) Visual and Electrosensory Circuits of the Diencephalon in Mormyrids: An Evolutionary Perspective MARIO F. WULLIMANN AND R. GLENN NORTHCUTT Georg-August-Universitat,Zentrum Anatomie, 3400 Gottingen, Federal Republic of Germany (M.F.W.); University of California, San Diego, and Department of Neurosciences A-001, Scripps Institution of Oceanography, La Jolla, California 92093 (R.G.N.) ABSTRACT Mormyrids are one of two groups of teleost fishes known to have evolved electroreception, and the concomitant neuroanatomical changes have confounded the interpretation of many of their brain areas in a comparative context, e.g., the diencephalon, where different sensory systems are processed and relayed. Recently, cerebellar and retinal connections of the diencephalon in mormyrids were reported. The present study reports on the telencephalic and tectal connections, specifically in Gnathonemus petersii, as these data are critical for an accurate interpretation of diencephalic nuclei in teleosts. Injections of horseradish peroxidase into the telencephalon retrogradely labeled neurons ipsilaterally in various thalamic, preglomer- ular, and tuberal nuclei, the nucleus of the locus coeruleus (also contralaterally), the superior raphe, and portions of the nucleus lateralis valvulae. Telencephalic injections anterogradely labeled the dorsal preglomerular and the dorsal tegmental nuclei bilaterally. Injections into the optic tectum retrogradely labeled neurons bilaterally in the central zone of area dorsalis telencephali and ipsilaterally in the torus longitudinalis, various thalamic, pretectal, and tegmental nuclei, some nuclei in the torus semicircularis, the nucleus of the locus coeruleus, the nucleus isthmi and the superior reticular formation, basal cells in the ipsilateral valvula cerebelli, and eurydendroid cells in the contralateral lobe C4 of the corpus cerebelli. -
Cortex and Thalamus Lecture.Pptx
Cerebral Cortex and Thalamus Hyperbrain Ch 2 Monica Vetter, PhD January 24, 2013 Learning Objectives: • Anatomy of the lobes of the cortex • Relationship of thalamus to cortex • Layers and connectivity of the cortex • Vascular supply to cortex • Understand the location and function of hypothalamus and pituitary • Anatomy of the basal ganglia • Primary functions of the different lobes/ cortical regions – neurological findings 1 Types of Cortex • Sensory (Primary) • Motor (Primary) • Unimodal association • Multimodal association - necessary for language, reason, plan, imagine, create Note: • Gyri • Sulci • Fissures • Lobes 2 The Thalamus is highly interconnected with the cerebral cortex, and handles most information traveling to or from the cortex. “Specific thalamic Ignore nuclei” – have well- names of defined sensory or thalamic nuclei for motor functions now - A few Other nuclei have will more distributed reappear later function 3 Thalamus Midbrain Pons Limbic lobe = cingulate gyrus Structure of Neocortex (6 layers) white matter gray matter Pyramidal cells 4 Connectivity of neurons in different cortical layers Afferents = inputs Efferents = outputs (reciprocal) brainstem etc Eg. Motor – Eg. Sensory – more efferent more afferent output input Cortico- cortical From Thalamus To spinal cord, brainstem etc. To Thalamus Afferent and efferent connections to different ….Depending on whether they have more layers of cortex afferent or efferent connections 5 Different areas of cortex were defined by differences in layer thickness, and size and -
Lesions in the Bed Nucleus of the Stria Terminalis Disrupt
Neuroscience 128 (2004) 7–14 LESIONS IN THE BED NUCLEUS OF THE STRIA TERMINALIS DISRUPT CORTICOSTERONE AND FREEZING RESPONSES ELICITED BY A CONTEXTUAL BUT NOT BY A SPECIFIC CUE-CONDITIONED FEAR STIMULUS G. M. SULLIVAN,a* J. APERGIS,b D. E. A. BUSH,b Activation of the hypothalamic–pituitary–adrenal (HPA) L. R. JOHNSON,b M. HOUb AND J. E. LEDOUXb axis, including release of glucocorticoids, is a central com- aDepartment of Psychiatry, Columbia University College of Physicians ponent of the adaptive response to real or anticipated and Surgeons, 1051 Riverside Drive, Unit #41, New York, NY 10032, aversive physical or psychological challenge. Surprisingly USA little is known about the neural circuits by which environ- bCenter for Neural Science, New York University, 4 Washington Place, mental stimuli come to elicit HPA responses. Fear condi- New York, NY 10003, USA tioning, a behavioral model of emotional stress, is poten- tially useful for exploring this issue since the neural path- Abstract —The bed nucleus of the stria terminalis (BNST) is ways by which stimuli initiate fear behaviors and believed to be a critical relay between the central nucleus of associated autonomic responses have been characterized the amygdala (CE) and the paraventricular nucleus of the in detail (LeDoux, 2000; Davis and Whalen, 2001; Maren, hypothalamus in the control of hypothalamic–pituitary– 2001). adrenal (HPA) responses elicited by conditioned fear stimuli. Through fear conditioning an organism learns that a If correct, lesions of CE or BNST should block expression of simple sensory stimulus (a cue), or more complex environ- HPA responses elicited by either a specific conditioned fear mental representation (a context), predicts imminent ad- cue or a conditioned context. -
Somatostatin in the Periventricular Nucleus of the Female Rat: Age Specific Effects of Estrogen and Onset of Reproductive Aging
4 Somatostatin in the Periventricular Nucleus of the Female Rat: Age Specific Effects of Estrogen and Onset of Reproductive Aging Eline M. Van der Beek, Harmke H. Van Vugt, Annelieke N. Schepens-Franke and Bert J.M. Van de Heijning Human and Animal Physiology Group, Dept. Animal Sciences, Wageningen University & Research Centre The Netherlands 1. Introduction The functioning of the growth hormone (GH) and reproductive axis is known to be closely related: both GH overexpression and GH-deficiency are associated with dramatic decreases in fertility (Bartke, 1999; Bartke et al, 1999; 2002; Naar et al, 1991). Also, aging results in significant changes in functionality of both axes within a similar time frame. In the rat, GH secretion patterns are clearly sexually dimorphic (Clark et al, 1987; Eden et al, 1979; Gatford et al, 1998). This has been suggested to result mainly from differences in somatostatin (SOM) release patterns from the median eminence (ME) (Gillies, 1997; Muller et al, 1999; Tannenbaum et al, 1990). SOM is synthesized in the periventricular nucleus of the hypothalamus (PeVN) and controls in concert with GH-releasing hormone (GHRH) the GH release from the pituitary (Gillies, 1987; Tannenbaum et al, 1990; Terry and Martin, 1981; Zeitler et al, 1991). An altered GH status is reflected in changes in the hypothalamic SOM system. For instance, the number of SOM cells (Sasaki et al, 1997) and pre-pro SOM mRNA levels (Hurley and Phelps, 1992) in the PeVN were elevated in animals overexpressing GH. Several observations suggest that SOM may also affect reproductive function directly at the level of the hypothalamus. -
The Effect of Fasting on the Ultrastructure of the Hypothalamic Arcuate Nucleus in Young Rats
Folia Morphol. Vol. 68, No. 3, pp. 113–118 Copyright © 2009 Via Medica O R I G I N A L A R T I C L E ISSN 0015–5659 www.fm.viamedica.pl The effect of fasting on the ultrastructure of the hypothalamic arcuate nucleus in young rats J. Kubasik-Juraniec1, N. Knap2 1Department of Electron Microscopy, Medical University of Gdańsk, Poland 2Department of Medical Chemistry, Medical University of Gdańsk, Poland [Received 8 May 2009; Accepted 17 July 2009] In the present study, we described ultrastructural changes occurring in the neurons of the hypothalamic arcuate nucleus after food deprivation. Young male Wistar rats (5 months old, n = 12) were divided into three groups. The animals in Group I were used as control (normally fed), and the rats in Groups II and III were fasted for 48 hours and 96 hours, respectively. In both treated groups, fasting caused rearrangement of the rough endoplasmic reticulum form- ing lamellar bodies and membranous whorls. The lamellar bodies were rather short in the controls, whereas in the fasting animals they became longer and were sometimes participating in the formation of membranous whorls com- posed of the concentric layers of the smooth endoplasmic reticulum. The whorls were often placed in the vicinity of a very well developed Golgi complex. Some Golgi complexes displayed an early stage of whorl formation. Moreover, an increased serum level of 8-isoprostanes, being a reliable marker of total oxida- tive stress in the body, was observed in both fasting groups of rats as com- pared to the control. (Folia Morphol 2009; 68, 3: 113–118) Key words: arcuate nucleus, fasting, membranous whorls, isoprostanes INTRODUCTION membranous whorls in the ARH neurons of a male The arcuate nucleus of the hypothalamus (ARH) rat on the fourth day after castration. -
Critical Role of Dorsomedial Hypothalamic Nucleus in a Wide Range of Behavioral Circadian Rhythms
The Journal of Neuroscience, November 19, 2003 • 23(33):10691–10702 • 10691 Behavioral/Systems/Cognitive Critical Role of Dorsomedial Hypothalamic Nucleus in a Wide Range of Behavioral Circadian Rhythms Thomas C. Chou,1,2 Thomas E. Scammell,2 Joshua J. Gooley,1,2 Stephanie E. Gaus,1,2 Clifford B. Saper,2 and Jun Lu2 1Department of Neurobiology and Program in Neuroscience, Harvard Medical School, Boston, Massachusetts 02115, and 2Department of Neurology, Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215 The suprachiasmatic nucleus (SCN) contains the brain’s circadian pacemaker, but mechanisms by which it controls circadian rhythms of sleep and related behaviors are poorly understood. Previous anatomic evidence has implicated the dorsomedial hypothalamic nucleus (DMH) in circadian control of sleep, but this hypothesis remains untested. We now show that excitotoxic lesions of the DMH reduce circadian rhythms of wakefulness, feeding, locomotor activity, and serum corticosteroid levels by 78–89% while also reducing their overall daily levels. We also show that the DMH receives both direct and indirect SCN inputs and sends a mainly GABAergic projection to the sleep-promoting ventrolateral preoptic nucleus, and a mainly glutamate–thyrotropin-releasing hormone projection to the wake- promoting lateral hypothalamic area, including orexin (hypocretin) neurons. Through these pathways, the DMH may influence a wide range of behavioral circadian rhythms. Key words: suprachiasmatic nucleus; sleep; feeding; corticosteroid; locomotor activity; melatonin Introduction sponses, in feeding, and in the circadian release of corticosteroids In many animals, the suprachiasmatic nucleus (SCN) strongly (for review, see Bellinger et al., 1976; Kalsbeek et al., 1996; Ber- influences circadian rhythms of sleep–wake behaviors, but the nardis and Bellinger, 1998; DiMicco et al., 2002), although many pathways mediating these influences are poorly understood. -
Regulation of the Neuroendocrine Reproductive Axis by Kisspeptin-GPR54 Signaling
REPRODUCTIONREVIEW Regulation of the neuroendocrine reproductive axis by kisspeptin-GPR54 signaling Jeremy T Smith1, Donald K Clifton2 and Robert A Steiner1,2 Departments of 1Physiology and Biophysics and 2Obstetrics and Gynecology, University of Washington, Seattle, Washington 98195-7290, USA Correspondence should be addressed to R A Steiner at Department of Physiology and Biophysics, Health Sciences Building, G-424, School of Medicine, University of Washington, Box no. 357290, Seattle, WA 98195-7290, USA; Email: [email protected] Abstract The Kiss1 gene codes for a family of peptides that act as endogenous ligands for the G protein-coupled receptor GPR54. Spontaneous mutations or targeted deletions of GPR54 in man and mice produce hypogonadotropic hypogonadism and infer- tility. Centrally administered kisspeptins stimulate gonadotropin secretion by acting directly on GnRH neurons. Sex steroids regulate the expression of KiSS-1 mRNA in the brain through direct action on KiSS-1 neurons. In the arcuate nucleus (Arc), sex steroids inhibit the expression of KiSS-1, suggesting that these neurons serve as a conduit for the negative feedback regulation of gonadotropin secretion. In the anteroventral periventricular nucleus (AVPV), sex steroids induce the expression of KiSS-1, implying that KiSS-1 neurons in this region may have a role in the preovulatory LH surge (in the female) or sexual behavior (in the male). Reproduction (2006) 131 623–630 Discovery essential to initiate gonadotropin secretion at puberty and support reproductive function in the adult. GPR54 is a G protein-coupled receptor, which was orig- inally identified as an ‘orphan’ receptor in the rat (Lee et al. 1999). Although GPR54 shares a modest sequence How Kiss1 got its name homology with the known galanin receptors, galanin Investigators at the Pennsylvania State College of Medi- apparently does not bind specifically to this receptor (Lee cine in Hershey, Pennsylvania, discovered the Kiss1 gene. -
The Connexions of the Amygdala
J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.28.2.137 on 1 April 1965. Downloaded from J. Neurol. Neurosurg. Psychiat., 1965, 28, 137 The connexions of the amygdala W. M. COWAN, G. RAISMAN, AND T. P. S. POWELL From the Department of Human Anatomy, University of Oxford The amygdaloid nuclei have been the subject of con- to what is known of the efferent connexions of the siderable interest in recent years and have been amygdala. studied with a variety of experimental techniques (cf. Gloor, 1960). From the anatomical point of view MATERIAL AND METHODS attention has been paid mainly to the efferent connexions of these nuclei (Adey and Meyer, 1952; The brains of 26 rats in which a variety of stereotactic or Lammers and Lohman, 1957; Hall, 1960; Nauta, surgical lesions had been placed in the diencephalon and and it is now that there basal forebrain areas were used in this study. Following 1961), generally accepted survival periods of five to seven days the animals were are two main efferent pathways from the amygdala, perfused with 10 % formol-saline and after further the well-known stria terminalis and a more diffuse fixation the brains were either embedded in paraffin wax ventral pathway, a component of the longitudinal or sectioned on a freezing microtome. All the brains were association bundle of the amygdala. It has not cut in the coronal plane, and from each a regularly spaced generally been recognized, however, that in studying series was stained, the paraffin sections according to the Protected by copyright. the efferent connexions of the amygdala it is essential original Nauta and Gygax (1951) technique and the frozen first to exclude a contribution to these pathways sections with the conventional Nauta (1957) method. -
The Effect of Lateral Hypothalamic Lesions on Spontaneous Eeg Pattern in Rats
ACTA NEUROBIOL. EXP. 1987, 47: 27-43 THE EFFECT OF LATERAL HYPOTHALAMIC LESIONS ON SPONTANEOUS EEG PATTERN IN RATS W. TROJNIAR, E. JURKOWLANIEC, J. ORZEL-GRYGLEWSKA and J. TOKARSKI Department of Physiology, Medical Academy Dqbinki 1, 80-211 Gdalisk, Poland Key words: lateral hypothalamus lesion, EEG, waking, sleep, subthalamus, somnolence Abstract. Neocortical and hippocampal EEG was recorded in ten rats subjected to bilateral lesions of the lateral hypothalamus at different levels of its rostro-caudal axis. In nine rats the damage evoked a marked increase of waking time with a si- multaneous reduction of the percentage of large amplitude irregular activity related to slow wave sleep in the first eight postlesion days. There was also a decrease in the amount of paradoxical sleep. Enhanced waking coexisted with behavioral som- nolence. The most extensive hypothalamic lesions produced qualitative changes of EEG concerning mainly the frequency of hippocampal theta rhythm. Control lesions within the subthalamic region did not influence either qualitative or quan- titative EEG pattern. It is concluded that limited lesions of the lateral hypotha- lamus did not destroy a sufficient number of reticular activating fibers to disturb a cortical desynchronizing reaction. The increased amount of waking pattern may be due to serotonergic deafferentation of the neocortex. Dissociation of behavioral and EEG indices of the level of arousal imply the existence of separate neuronal systems for both aspects of "activation". Bilateral destruction of the lateral hypothalamus (LH), particularly in its middle portion produces a set of severe abnormalities known as "the lateral hypothalamic syndrome". The animals, both rats and cats, display, among others, profound impairments in food and water intake (1, 32), deficits in sensorimotor integration (16), somnolence, akinesia and catalepsy (14). -
Hypothalamic Hypocretin (Orexin): Robust Innervation of the Spinal Cord
The Journal of Neuroscience, April 15, 1999, 19(8):3171–3182 Hypothalamic Hypocretin (Orexin): Robust Innervation of the Spinal Cord Anthony N. van den Pol Department of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut 06520 Hypocretin (orexin) is synthesized by neurons in the lateral chemistry support the concept that hypocretin-immunoreactive hypothalamus and has been reported to increase food intake fibers in the cord originate from the neurons in the lateral and regulate the neuroendocrine system. In the present paper, hypothalamus. Digital-imaging physiological studies with fura-2 long descending axonal projections that contain hypocretin detected a rise in intracellular calcium in response to hypocretin were found that innervate all levels of the spinal cord from in cultured rat spinal cord neurons, indicating that spinal cord cervical to sacral segments, as studied in mouse, rat, and neurons express hypocretin-responsive receptors. A greater human spinal cord and not previously described. High densities number of cervical cord neurons responded to hypocretin than of axonal innervation are found in regions of the spinal cord another hypothalamo-spinal neuropeptide, oxytocin. These related to modulation of sensation and pain, notably in the data suggest that in addition to possible roles in feeding and marginal zone (lamina 1). Innervation of the intermediolateral endocrine regulation, the descending hypocretin fiber system column and lamina 10 as well as strong innervation of the may play a role in modulation of sensory input, particularly in caudal region of the sacral cord suggest that hypocretin may regions of the cord related to pain perception and autonomic participate in the regulation of both the sympathetic and para- tone.