DOCSLIB.ORG

Optogenetic Mapping of Feeding and Self-Stimulation Within the Lateral

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Optogenetic Mapping of Feeding and Self-Stimulation Within the Lateral bioRxiv preprint doi: https://doi.org/10.1101/802405; this version posted October 11, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. 1 1 2 3 4 5 6 7 8 Optogenetic mapping of feeding and self-stimulation within 9 the lateral hypothalamus of the rat 10 11 Short title: Optogenetic behavior mapping in the lateral hypothalamus 12 13 Kevin R. Urstadt#a *, Kent C. Berridge 14 Psychology Dept., University of Michigan 15 1004 East Hall, 530 Church Street 16 Ann Arbor, Michigan, U.S.A. 48109-1043 17 18 #a Current address: 19 Cognitive Science Dept., Occidental College 20 1600 Campus Road 21 Los Angeles, California, U.S.A. 90041 22 23 * Corresponding author 24 Email: [email protected] (KRU) 25 bioRxiv preprint doi: https://doi.org/10.1101/802405; this version posted October 11, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. 2 26 27 Abstract 28 The lateral hypothalamus (LH) regulates eating and motivation, and includes several 29 anatomical subregions. This study explored localization of function across different LH 30 subregions in controlling food intake stimulated by optogenetic channelrhodopsin excitation, and 31 in supporting laser self-stimulation. We particularly compared the tuberal LH, the posterior LH, 32 and the lateral preoptic area. Local diameters of tissue optogenetically stimulated within LH 33 were assessed by measuring laser-induced Fos plumes and Jun plumes via 34 immunofluorescence surrounding optic fiber tips, and were used to map localization of function 35 for effects elicited by LH optogenetic stimulation. Optogenetic stimulation of the tuberal 36 subsection of the LH behaviorally produced the most robust food intake initially, but produced 37 only mild laser self-stimulation in the same rats. However, after repeated exposures to 38 optogenetic stimulation, tuberal LH behavioral profiles shifted toward more self-stimulation and 39 less food intake. By contrast, stimulation of the lateral preoptic area produced relatively little 40 food intake or self-stimulation, either initially or after extended stimulation experience. 41 Stimulation in the posterior LH subregion supported moderate self-stimulation, but not food 42 intake here, and at higher laser intensity shifted valence to evoke escape behaviors. We 43 conclude that the tuberal LH subregion may best mediate increases in food intake stimulated by 44 optogenetic excitation. However, incentive motivational effects of tuberal LH stimulation may 45 shift toward self-stimulation behavior after repeated stimulation. By contrast, the lateral preoptic 46 area and posterior LH do not as readily elicit either eating behavior or laser self-stimulation, and 47 may be more prone to higher-intensity aversive effects. 48 bioRxiv preprint doi: https://doi.org/10.1101/802405; this version posted October 11, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. 3 49 Introduction 50 The lateral hypothalamus (LH) has been considered a powerful regulator of food 51 ingestion and reward-seeking motivation for over 60 years (1). Today the LH remains a prime 52 target of research into obesity, anorexia, and reward-related motivational dysfunctions (2). Early 53 decades of research used lesion, electrical stimulation, electrophysiological recording, and 54 intracranial microinjection techniques, whereas many contemporary studies have shifted to 55 optogenetic, DREADD, and optical imaging techniques. 56 The LH was first anatomically described nearly a century ago (3,4). Electrolytic LH 57 lesions were soon known to result in aphagia, adipsia, and sensory neglect behaviors (5–8). 58 Further, in early studies large LH lesions also produced pathological excessive ‘disgust’, evident 59 as gapes, headshakes and chin rubs that are normally elicited only by bitter or other unpalatable 60 tastes, becoming elicited by the taste of sucrose (7,9,10). However, subsequent excitotoxin 61 lesion studies showed that the site where neuron loss produced ‘disgust’ is actually in 62 caudolateral ventral pallidum, anterior to LH, and not in LH itself (11,12). LH lesions that do not 63 damage the ventral pallidum, as well as neurotoxic destruction of dopamine fibers of passage 64 through LH, do produce aphagia and sensory neglect, but not excessive ‘disgust’ ((7,8,11,13– 65 16). These lesion data paint a strong necessity role for the LH in intake, while neighboring 66 regions and fibers passing through the LH control a broader range of reward, disgust, and 67 motivation-related functions. 68 Other electrical stimulation experiments demonstrated that LH activation elicits eating, 69 drinking and other natural motivated behaviors (17). Additionally, rats were typically willing to 70 self-stimulate or work to activate the same LH electrodes, implicating the LH in both hunger and 71 reward (17–21). However, for most LH stimulation effects, there was not clear localization of 72 function within the LH (17). Conceivably, stimulation of fibers of passage by an LH electrode 73 may also play a role in behavioral effects, which could possibly obscure localization of function bioRxiv preprint doi: https://doi.org/10.1101/802405; this version posted October 11, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. 4 74 within subregional clusters of LH neurons (22,23), making it difficult to specify the relative 75 contribution of intrinsic LH neurons. The possibility of localization of function within LH for 76 neuronal stimulation effects could yet emerge, if explored with modern techniques, such as 77 optogenetic stimulation of neurons in particular LH subregions. 78 Beyond the question of subregional LH differences in localization of function, another 79 important issue is the permanence versus malleability of behavioral effects of LH stimulation. 80 For example, using electrode stimulation in the LH, Valenstein and colleagues (24) showed that 81 the behavior evoked from rats by LH stimulation could change over time, due to repeated 82 experiences with electrical LH stimulation (Cox and Valenstein, 1969). For example, some LH 83 stimulation sites did not initially evoke eating, but subsequently did after rats received prolonged 84 exposures to electrode stimulation overnight while in a food deprived state (25). For other rats, 85 the dominant type of behavior elicited by LH stimulation switched from LH-evoked eating to LH- 86 evoked drinking in the same rats, after repeated experiences with LH stimulation in which food 87 targets were removed but water was available (26). Later when food was returned and a choice 88 was available, those rats remained stimulation-bound drinkers. Such reports suggest the 89 possibility that repeated experience might also possibly change the type of behavior evoked by 90 LH optogenetic neuronal stimulation. 91 To address these issues, we utilized optogenetic channelrhodopsin (ChR2) stimulation 92 to excite neurons in specific LH subregions of different rats. Excitation of LH neurons in specific 93 subregions, without stimulating fibers of passage, was assessed both for laser self-stimulation 94 and for stimulation-bound increases in eating. We also mapped potential localization of function. 95 In order to identify how large a subregion of LH was activated by ChR2 stimulation, which is 96 information required to assign localization of function, we measured immunofluorescence of 97 local Fos plumes induced by laser illumination around an optic fiber tip, and compared their 98 sizes to those of corresponding Jun plumes. Additionally, we assessed if any laser-evoked 99 behaviors changed after a phase of extended experience with LH optogenetic stimulation. bioRxiv preprint doi: https://doi.org/10.1101/802405; this version posted October 11, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. 5 100 101 Methods and materials 102 Subjects 103 Pair-housed adult Sprague-Dawley rats (Rattus norvegicus; N=32; male NChR2 = 10; 104 male NeYFP = 6; female NChR2 = 11; female NeYFP = 5) weighing 250-400 g at the time of surgery 105 were maintained on a reverse 12 hr light-dark cycle at 21°C. Rats were always provided ad 106 libitum access to standard Purina rat chow and to water in home cages unless otherwise 107 specified. Males and females were housed in separate rooms, tested separately, and test 108 chambers were cleaned between uses to prevent sexual odor cues from influencing behavior. 109 Animal use procedures were approved by the Institutional Animal Care and Use Committee at 110 the University of Michigan. 111 Surgery 112 Rats were anesthetized with ketamine (100 mg/kg, i.p.) and xylazine (7 mg/kg, i.p.) and 113 were given atropine (0.04 mg/kg, i.p.), carprofen (5 mg/kg, s.c.), cefazolin (60 mg/kg, s.c.), and 114 isotonic saline (2 mL, s.c.) intraoperatively to prevent respiratory occlusion, inflammation, 115 infection, and dehydration, respectively. Using a stereotaxic apparatus, rats received surgical 116 microinjections of either an AAV5 virus containing genes for channelrhodopsin (ChR2) for 117 optogenetic stimulation, an enhanced yellow fluorescence protein (eYFP) reporter, and hSyn 118 promoter (AAV5 hSyn-ChR2-eYFP), or of an optically-inactive control virus, containing genes 119 only for hSyn promoter and eYFP reporter (AAV5 hSyn-eYFP).
Load more

Recommended publications
  • 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).
    [Show full text]
  • 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.
    [Show full text]
  • Tonic Activity in Lateral Habenula Neurons Promotes Disengagement from Reward-Seeking Behavior
    bioRxiv preprint doi: https://doi.org/10.1101/2021.01.15.426914; this version posted January 16, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. Tonic activity in lateral habenula neurons promotes disengagement from reward-seeking behavior 5 Brianna J. Sleezer1,3, Ryan J. Post1,2,3, David A. Bulkin1,2,3, R. Becket Ebitz4, Vladlena Lee1, Kasey Han1, Melissa R. Warden1,2,5,* 1Department of Neurobiology and Behavior, Cornell University, Ithaca, NY 14853, USA 2Cornell Neurotech, Cornell University, Ithaca, NY 14853 USA 10 3These authors contributed equally 4Department oF Neuroscience, Université de Montréal, Montréal, QC H3T 1J4, Canada 5Lead Contact *Correspondence: [email protected] 15 Sleezer*, Post*, Bulkin* et al. 1 of 38 bioRxiv preprint doi: https://doi.org/10.1101/2021.01.15.426914; this version posted January 16, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. SUMMARY Survival requires both the ability to persistently pursue goals and the ability to determine when it is time to stop, an adaptive balance of perseverance and disengagement. Neural activity in the 5 lateral habenula (LHb) has been linked to aversion and negative valence, but its role in regulating the balance between reward-seeking and disengaged behavioral states remains unclear.
    [Show full text]
  • Brain Structure and Function Related to Headache
    Review Cephalalgia 0(0) 1–26 ! International Headache Society 2018 Brain structure and function related Reprints and permissions: sagepub.co.uk/journalsPermissions.nav to headache: Brainstem structure and DOI: 10.1177/0333102418784698 function in headache journals.sagepub.com/home/cep Marta Vila-Pueyo1 , Jan Hoffmann2 , Marcela Romero-Reyes3 and Simon Akerman3 Abstract Objective: To review and discuss the literature relevant to the role of brainstem structure and function in headache. Background: Primary headache disorders, such as migraine and cluster headache, are considered disorders of the brain. As well as head-related pain, these headache disorders are also associated with other neurological symptoms, such as those related to sensory, homeostatic, autonomic, cognitive and affective processing that can all occur before, during or even after headache has ceased. Many imaging studies demonstrate activation in brainstem areas that appear specifically associated with headache disorders, especially migraine, which may be related to the mechanisms of many of these symptoms. This is further supported by preclinical studies, which demonstrate that modulation of specific brainstem nuclei alters sensory processing relevant to these symptoms, including headache, cranial autonomic responses and homeostatic mechanisms. Review focus: This review will specifically focus on the role of brainstem structures relevant to primary headaches, including medullary, pontine, and midbrain, and describe their functional role and how they relate to mechanisms
    [Show full text]
  • Mapping the Populations of Neurotensin Neurons in the Male Mouse Brain T Laura E
    Neuropeptides 76 (2019) 101930 Contents lists available at ScienceDirect Neuropeptides journal homepage: www.elsevier.com/locate/npep Mapping the populations of neurotensin neurons in the male mouse brain T Laura E. Schroeder, Ryan Furdock, Cristina Rivera Quiles, Gizem Kurt, Patricia Perez-Bonilla, ⁎ Angela Garcia, Crystal Colon-Ortiz, Juliette Brown, Raluca Bugescu, Gina M. Leinninger Department of Physiology, Michigan State University, East Lansing, MI 48114, United States ARTICLE INFO ABSTRACT Keywords: Neurotensin (Nts) is a neuropeptide implicated in the regulation of many facets of physiology, including car- Lateral hypothalamus diovascular tone, pain processing, ingestive behaviors, locomotor drive, sleep, addiction and social behaviors. Parabrachial nucleus Yet, there is incomplete understanding about how the various populations of Nts neurons distributed throughout Periaqueductal gray the brain mediate such physiology. This knowledge gap largely stemmed from the inability to simultaneously Central amygdala identify Nts cell bodies and manipulate them in vivo. One means of overcoming this obstacle is to study NtsCre Thalamus mice crossed onto a Cre-inducible green fluorescent reporter line (NtsCre;GFP mice), as these mice permit both Nucleus accumbens Preoptic area visualization and in vivo modulation of specific populations of Nts neurons (using Cre-inducible viral and genetic tools) to reveal their function. Here we provide a comprehensive characterization of the distribution and relative Abbreviation: 12 N, Hypoglossal nucleus;
    [Show full text]
  • The Lateral Hypothalamic Parvalbuminimmunoreactive
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE Published in "7KH-RXUQDORI&RPSDUDWLYH1HXURORJ\ GRLFQH" provided by RERO DOC Digital Library which should be cited to refer to this work. The lateral hypothalamic parvalbumin-immunoreactive (PV1) nucleus in rodents* Zoltán Mészár1, Franck Girard1, Clifford B. Saper2 and Marco R. Celio1,2** 1Anatomy Unit and “Program in Neurosciences”, Department of Medicine, University of Fribourg, Rte. A. Gockel 1, CH-1700 Fribourg, Switzerland 2 Neurology and Neuroscience, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA Running title: Parvalbumin-positive nucleus in the lateral hypothalamus Associate Editor: Paul W. Sawchenko Key Words: medial forebrain bundle, lateral tuberal nucleus, glutamate, projection neurons, neuropeptides, vocalization Corresponding author: Marco R. Celio, Anatomy and “Program in Neuroscience”, Department of Medicine, University of Fribourg, Rte. A. Gockel 1, CH-1700 Fribourg, Switzerland. Phone: +41 26 300 84 91; Fax: +41 26 300 97 33. E-mail: http://doc.rero.ch [email protected]. **MRC spent sabbatical leaves at HMS in 1997 and 2008. Supported by the Canton of Fribourg, an grant of the Swiss National Science Foundation (no.: 3100A0-113524), the Novartis Foundation and USPHS grants NS33987 and NS072337. *Dedicated to Emilio Celio (1927-2011), founder of Swant. Abbreviations: Anatomic: IIn: optic nerve 3dV: third ventricle 2 A: amygdala AHA: anterior hypothalamic area Cer: cerebellum cp: cerebral peduncle DMH: dorsomedial hypothalamic
    [Show full text]
  • The Neuromodulatory Basis of Emotion
    1 The Neuromodulatory Basis of Emotion Jean-Marc Fellous Computational Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, California The Neuroscientist 5(5):283-294,1999. The neural basis of emotion can be found in both the neural computation and the neuromodulation of the neural substrate mediating behavior. I review the experimental evidence showing the involvement of the hypothalamus, the amygdala and the prefrontal cortex in emotion. For each of these structures, I show the important role of various neuromodulatory systems in mediating emotional behavior. Generalizing, I suggest that behavioral complexity is partly due to the diversity and intensity of neuromodulation and hence depends on emotional contexts. Rooting the emotional state in neuromodulatory phenomena allows for its quantitative and scientific study and possibly its characterization. Key Words: Neuromodulation, Emotion, Affect, Hypothalamus, Amygdala, Prefrontal the behavior1 that this substrate mediates. The Introduction neuromodulation of 'cognitive centers' results in phenomena pertaining to emotional influences of The scientific study of the neural basis of cognitive processing. Neuromodulations of memory emotion is an active field of experimental and structures explain the influence of emotion on theoretical research (See (1,2) for reviews). Partly learning and recall; the neuromodulation of specific because of a lack of a clear definition (should it reflex pathways explains the influence of the exists) of what emotion is, and probably because of emotional state on elementary motor behaviors, and its complexity, it has been difficult to offer a so forth... neuroscience framework in which the influence of The instantaneous pattern of such modulations emotion on behavior can be studied in a (i.e.
    [Show full text]
  • Categorization of Neurons in the Lateral Hypothalamus by Projection and Morphology
    Categorization of Neurons in the Lateral Hypothalamus by Projection and Morphology Elin Hermann [email protected] under the direction of Prof. Konstantinos Meletis PhD. Daniela Calvigioni PhD. Janós Fuzik Department of Neuroscience Karolinska Institutet Research Academy for Young Scientists July 11, 2018 Abstract To cure brain disorders scientists must figure out how the brain functions. Thus the aim of this study is to see which neurons in the lateral hypothalamus (LHA) are connected to the Lateral habenula (LHb) and to periaqueductal gray (PAG). Additionally, the diver- sity of neurons will be investigated by projection and morphology in order to categorize neurons in the LHA. Retrograde injections were administrated in the LHb and PAG, re- constructions of the morphology of some neurons was performed. Immunohistochemistry with melanin-concentrating hormone (MCH), parvalbumin (PV), and estrogen (ER) in the LHA were conducted in different coordinates of the brain. It was shown that MCH varied in different coordinates, that PV marked neurons barely existed in the LHA and neurons with ER were common in the LHA area. Furthermore, the reconstruction of cell morphology showed two different-looking neurons projected to the LHb. One type looked similar to the neurons projecting to the PAG and the other had a simpler morphology. Future studies need to be performed in order to aquire more accurate results of both the reconstruction and the staining with immunohistochemistry to prove their reliability. Additionally, immunohistochemistry of the two different neurons projected to the LHb should be done in order to see a difference and potentially categorize them. Acknowledgements I would like to thank Prof.
    [Show full text]
  • Inhibitory Input from the Lateral Hypothalamus to the Ventral Tegmental Area Disinhibits Dopamine Neurons and Promotes Behavioral Activation
    Inhibitory Input from the Lateral Hypothalamus to the Ventral Tegmental Area Disinhibits Dopamine Neurons and Promotes Behavioral Activation The MIT Faculty has made this article openly available. Please share how this access benefits you. Your story matters. Citation Nieh, Edward H. et al. “Inhibitory Input from the Lateral Hypothalamus to the Ventral Tegmental Area Disinhibits Dopamine Neurons and Promotes Behavioral Activation.” Neuron 90, 6 (June 2016): 1286–1298 © 2016 Elsevier Inc As Published http://dx.doi.org/10.1016/J.NEURON.2016.04.035 Publisher Elsevier/Cell Press Version Author's final manuscript Citable link http://hdl.handle.net/1721.1/112706 Terms of Use Creative Commons Attribution-NonCommercial-NoDerivs License Detailed Terms http://creativecommons.org/licenses/by-nc-nd/4.0/ HHS Public Access Author manuscript Author ManuscriptAuthor Manuscript Author Neuron. Manuscript Author Author manuscript; Manuscript Author available in PMC 2017 June 15. Published in final edited form as: Neuron. 2016 June 15; 90(6): 1286–1298. doi:10.1016/j.neuron.2016.04.035. Inhibitory Input from the Lateral Hypothalamus to the Ventral Tegmental Area Disinhibits Dopamine Neurons and Promotes Behavioral Activation Edward H. Nieh1,2, Caitlin M. Vander Weele1,2, Gillian A. Matthews1, Kara N. Presbrey1, Romy Wichmann1, Christopher A. Leppla1, Ehsan M. Izadmehr1, and Kay M. Tye1,* 1The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA SUMMARY Projections from the lateral hypothalamus (LH) to the ventral tegmental area (VTA), containing both GABAergic and glutamatergic components, encode conditioned responses and control compulsive reward-seeking behavior.
    [Show full text]
  • Anatomy of the Opioid-Systems of the Brain Karl M
    THE CANADIAN JOURNAL OF NEUROLOGICAL SCIENCES SPECIAL FEATURE Anatomy of the Opioid-Systems of the Brain Karl M. Knigge and Shirley A. Joseph This paper was presented in May 1983 at the Centennial Neurosciences Symposium of the Department of Anatomy, University of Manitoba, at which Dr. Knigge was a keynote speaker. Can. J. Neurol. Sci. 1984; 11:14-23 In 1969, Roger Guillemin and Andrew Schally independently subpopulations: a hypothalamic arcuate opiocortin system, a reported the isolation and identification of the first hypothalamic brainstem medullary opiocortin pool of neurons, and a hypo­ neuropeptide, thyrotropin releasing factor (TRF). Following thalamic alpha MSH-specific system. In the present report we this landmark event in neuroendocrinology the ensuing years will review our anatomical studies on only the opiocortin division have witnessed a cascade of isolations of new neuropeptides of the brain opioids. Unless specifically noted, our descriptions and a virtual revolution in neurobiology. The discipline of relate to the brain of the rat. neuroendocrinology has been remarkably impacted by the The arcuate opiocortin system consists of a pool or "bed nucleus" evidence that all of the "hypophysiotrophic" releasing factors of perikarya located in the arcuate and periarcuate regions of presently identified are distributed widely throughout the brain the hypothalamus (Fig. 1). In species we have examined, including with neurotransmitter or neuromodulator roles quite different rat, mouse, hamster, guinea pig, dog, horse, primate and human, from their actions of regulating the secretion of pituitary hormones. this pool of neuron cell bodies extends the entire antero-posterior The study of these neuropeptide systems in activity of the distance of the hypothalamus.
    [Show full text]
  • Hypothalamus
    883 Hypothalamus HYPOTHALAMUS Introduction The hypothalamus is a very small, but extremely important part of the diencephalon that is involved in the mediation of endocrine, autonomic and behavioral functions. The hypothalamus: (1) controls the release of 8 major hormones by the hypophysis, and is involved in (2) temperature regulation, (3) control of food and water intake, (4) sexual behavior and reproduction, (5) control of daily cycles in physiological state and behavior, and (6) mediation of emotional responses. A large number of nuclei and fiber tracts have been described in the hypothalamus. Some of these are ill-defined and have no known function, while others have been studied in detail both anatomically and physiologically. This handout will attempt to focus your attention on the significant and interesting aspects of the structure and function of the hypothalamus. The hypothalamus is the ventral-most part of the diencephalon. As seen in Fig. 2 of the thalamus handout, the hypothalamus is on either side of the third ventricle, with the hypothalamic sulcus delineating its dorsal border. The ventral aspect of the hypothalamus is exposed on the base of the brain (Fig. 1). It extends from the rostral limit of the optic chiasm to the caudal limit of the mammillary bodies. Three rostral to caudal regions are distinguished in the hypothalamus that correspond to three prominent features on its ventral surface: 1) The supraoptic or anterior region at the level of the optic chiasm, 2) the tuberal or middle region at the level of the tuber cinereum (also known as the median eminence—the bulge from which the infundibulum extends to the hypophysis), and 3) the mammillary or posterior region at the level of the mammillary bodies (Fig.
    [Show full text]
  • The Basolateral Amygdala and Lateral Hypothalamus Bias Learning
    Available online at www.sciencedirect.com ScienceDirect The basolateral amygdala and lateral hypothalamus bias learning towards motivationally significant events Ivy B Hoang and Melissa J Sharpe Every day we are faced with a huge amount of new information. best facilitate arrival at our eventual goal. Dysfunction in We can’t learn about everything, we have to select what to learn the balance between learning about proximal and distal about. We have many systems that contribute to learning in predictors of outcomes plays an important role in psycho- different ways, allowing us to select the most relevant logical disorders like anxiety, addiction, and schizophre- information to learn about. This review will focus on one such nia [1,2]. system, comprising the basolateral amygdala and lateral hypothalamus, which we argue works to favor learning about Two regions of the brain that are important for learning information most relevant to current goals. Specifically, we will about motivationally significant outcomes are the lateral discuss work that has revealed the role of the basolateral hypothalamus (LH) and the basolateral amygdala (BLA). amygdala in encoding the sensory-specific aspects of Both structures encode information that is proximal to rewarding information. Then, we discuss new data implicating food (or pain, under some conditions [10 ]), which facil- lateral hypothalamus in biasing learning towards reward- itates the ability to respond appropriately to these pre- predictive cues, and away from information distal to rewards. dictors in the future [3–8,9 ,10 ]. Yet when it comes to Finally, we offer a framework of how these regions learning about the distal predictors of food outcomes, the communicate to relay this information to the midbrain function of these regions diverges.
    [Show full text]