Mesolimbic Dopamine Neurons

Total Page:16

File Type:pdf, Size:1020Kb

Mesolimbic Dopamine Neurons Proc. Natl. Acad. Sci. USA Vol. 93, pp. 11202-11207, October 1996 Neurobiology Chronic morphine induces visible changes in the morphology of mesolimbic dopamine neurons (opiate addiction/brain-derived neurotrophic factor/tyrosine hydroxylase/Lucifer yellow/mesolimbic dopamine system) LioRA SKLAIR TAVRON*, WEI-XING SHI, SARAH B. LANE, HERBERT W. HARRISt, BENJAMIN S. BUNNEY, AND ERIC J. NESTLERt Laboratory of Molecular Psychiatry, Departments of Psychiatry and Pharmacology, Yale University School of Medicine and Connecticut Mental Health Center, 34 Park Street, New Haven, CT 06508 Communicated by Paul Greengard, Rockefeller University, New York NY July 5, 1996 (received for review May 21, 1996) ABSTRACT The mesolimbic dopamine system, which structural changes within this brain region (12, 13). Indirect arises in the ventral tegmental area (VTA), is an important support for this possibility is provided by the observation that neural substrate for opiate reinforcement and addiction. chronic morphine treatment results in a 50% impairment in Chronic exposure to opiates is known to produce biochemical axoplasmic transport from the VTA to a major forebrain adaptations in this brain region. We now show that these target, with no change in transport observed in other neural adaptations are associated with structural changes in VTA pathways studied (14). Moreover, intra-VTA infusion of brain- dopamine neurons. Individual VTA neurons in paraformal- derived neurotrophic factor (BDNF) or related neurotrophins, dehyde-fixed brain sections from control or morphine-treated known to support the survival of dopaminergic neurons in cell rats were injected with the fluorescent dye Lucifer yellow. The culture (see Discussion), has been shown recently to prevent identity of the injected cells as dopaminergic or nondopam- the morphine-induced biochemical adaptations in this brain inergic was determined by immunohistochemical labeling of region (15). the sections for tyrosine hydroxylase. Chronic morphine The goal of the present study was to assess directly whether treatment resulted in a mean -25% reduction in the area and the various biochemical adaptations elicited in the VTA by perimeter of VTA dopamine neurons. This reduction in cell chronic morphine administration are associated with morpho- size was prevented by concomitant treatment of rats with logical changes in this brain region. We show here that chronic naltrexone, an opioid receptor antagonist, as well as by exposure to morphine elicits a selective reduction in the size of intra-VTA infusion of brain-derived neurotrophic factor. In VTA dopamine neurons, with no change observed in nondo- contrast, chronic morphine treatment did not alter the size of paminergic neurons in this brain region. Moreover, the reduc- nondopaminergic neurons in the VTA, nor did it affect the tion in size of VTA dopamine neurons is prevented by intra- total number of dopaminergic neurons in this brain region. VTA infusion of BDNF. The results of these studies provide direct evidence for struc- tural alterations in VTA dopamine neurons as a consequence of chronic opiate exposure, which could contribute to changes MATERIALS AND METHODS in mesolimbic dopamine function associated with addiction. In Vivo Drug Treatments. Sprague-Dawley rats (initial weight 100-120 g; Camm Research Institute, Wayne, NJ) were Dopaminergic neurons in the ventral tegmental area (VTA) used in these studies. Morphine was administered chronically, and their projections to the limbic forebrain are important as described (5), by daily subcutaneous implantation of mor- neural substrates for the acute reinforcing properties of opiates phine pellets (containing 75 mg of morphine base; National and other drugs of abuse (1-4). It has been proposed that Institute on Drug Abuse) for 5 days under light halothane chronic exposure to a drug of abuse elicits long-lasting adap- anesthesia. Rats were used 24 hr after the last pellet implan- tations within these same brain regions that underlie changes tation. This treatment paradigm produces morphine tolerance in drug reinforcement mechanisms, as well as drug craving, and dependence based on behavioral, electrophysiological, associated with drug addiction. and biochemical criteria (see ref. 5). Control rats received Among the most consistent drug-induced adaptations in the equivalent implantation of placebo pellets. VTA is induction of tyrosine hydroxylase (TH; refs. 5-8), the Naltrexone (Sigma) was administered daily [50 mg/ml i.p. in rate-limiting enzyme in the biosynthesis of dopamine. In saline and 50 mg/ml in an emulsion of saline and lipid] addition, chronic morphine administration has been shown to immediately before morphine or placebo pellet implantation decrease levels of the three major neurofilament proteins, as described (10). This treatment paradigm has been shown to NF200, NF160, and NF68 (9), and to increase levels of glial completely block the development of morphine tolerance and fibrillary acidic protein (10) in this brain region. Each of these dependence based on behavioral, electrophysiological, and biochemical adaptations occurs specifically in the VTA and is biochemical criteria (see ref. 10). not elicited by chronic exposure to other psychotropic drugs BDNF was provided by Ronald Lindsay (Regeneron Phar- that lack reinforcing properties. In addition, similar adapta- maceuticals, Tarrytown, NY). It was infused at a dose of 2 tions in the VTA are observed in rats after chronic heroin ,ug/day (in 1QmM sodium phosphate, pH 7.4/0.9% NaCl/1% self-administration, indicating that they are induced in re- bovine serum albumin) directly into the VTA by osmotic sponse to self-regulated drug intake (11). minipumps via midline cannulae exactly as described (15). This The lower levels of neurofilament proteins and the recip- rocal increase in glial fibrillary acidic protein present in the Abbreviations: VTA, ventral tegmental area; TH, tyrosine hydroxy- VTA after chronic opiate administration raises the possibility lase; BDNF, brain-derived neurotrophic factor. that chronic exposure to opiates may result in prominent *Present address: Technion Institute of Technology, Bat-Galim, Haifa 31096, Israel. tPresent address: National Institute on Aging, National Institutes of The publication costs of this article were defrayed in part by page charge Health, Bethesda, MD 20892. payment. This article must therefore be hereby marked "advertisement" in ITo whom reprint requests should be addressed. e-mail: eric_nestler@ accordance with 18 U.S.C. §1734 solely to indicate this fact. qm.yale.edu. 11202 Downloaded by guest on September 25, 2021 Neurobiology: Sklair-Tavron et al. Proc. Natl. Acad. Sci. USA 93 (1996) 11203 BDNF dose has been shown to prevent many of the biochem- gated video camera. The morphological parameters of the ical effects elicited in the VTA by chronic morphine administra- neurons were measured by National Institutes of Health IMAGE tion (15). Control rats received intra-VTA infusions of vehicle. version 1.57 software; this was done with the experimenter Measurements of VTA Neuronal Morphology. The mor- blinded to the identity of the neurons as TH+ or TH- and of phology of VTA neurons was assessed by filling individual cells the slices as control or morphine-treated. Cell perimeter and with Lucifer yellow by use of a procedure based on previous area were then calculated. studies (16-19). Rats were deeply anesthetized with chloral In pilot experiments, 400-gm thick oblique midbrain slices hydrate (400 mg/kg i.p.) and then perfused transcardially with containing the VTA from control and morphine-treated rats 50 ml of ice-cold phosphate-buffered saline (PBS), followed by were prepared as described (21). Dopamine neurons, identi- 200 ml of 4% paraformaldehyde in PBS at a rate of 15 ml/min. fied by well-established electrophysiological criteria (for ex- Brains were removed and 100- to 150-,um thick oblique slices ample, see refs. 16 and 21), were recorded in whole cell mode (described below) were obtained through the VTA by use of with electrodes filled with an intracellular solution containing a vibratome. Neurons in the fixed slices were injected with 1% Lucifer yellow. The electrodes were withdrawn after 15 Lucifer yellow under an upright fluorescence microscope. min in cell-attached mode. One to two neurons were injected Individual neurons were visualized with Nomarski optics, per slice. The slices were then fixed in 4% paraformaldehyde, impaled with a glass microelectrode filled with 0.2% Lucifer cut into 50- to 100-gm thick sections, and mounted for analysis yellow in PBS, and injected by applying negative current pulses of cell morphology as described above. (2 Hz, 400 msec, 1 nA) for 5-10 min. After filling 4-8 cells per Counting VTA Dopamine Neurons. Control and morphine- slice, the slices were fixed in 4% paraformaldehyde in PBS treated rats were perfused with paraformaldehyde, as de- overnight at 4°C. scribed above. TH immunohistochemistry was then conducted Oblique brain slices, illustrated in Fig. 1, were used in these on fixed 40-gm thick coronal brain sections, and the number studies according to published procedures (21). In these of TH+ neurons was counted at x400 magnification, exactly as oblique slices, VTA dopamine neurons can be readily distin- described (22). Briefly, TH+ neurons were counted in every guished from substantia nigra dopamine neurons as being 40-,um section throughout the rostral-caudal extent of the located medial to the medial terminal nucleus of the
Recommended publications
  • Prominent Activation of Brainstem and Pallidal Afferents of the Ventral Tegmental Area by Cocaine
    Neuropsychopharmacology (2008) 33, 2688–2700 & 2008 Nature Publishing Group All rights reserved 0893-133X/08 $30.00 www.neuropsychopharmacology.org Prominent Activation of Brainstem and Pallidal Afferents of the Ventral Tegmental Area by Cocaine 1,3 2 1 1 1 Stefanie Geisler , Michela Marinelli , Beth DeGarmo , Mary L Becker , Alexander J Freiman , 2 2 ,1 Mitch Beales , Gloria E Meredith and Daniel S Zahm* 1 2 Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, St Louis, MO, USA; Department of Cellular & Molecular Pharmacology, Rosalind Franklin University of Medicine and Science, North Chicago, IL, USA Blockade of monoamine transporters by cocaine should not necessarily lead to certain observed consequences of cocaine administration, including increased firing of ventral mesencephalic dopamine (DA) neurons and accompanying impulse-stimulated release of DA in the forebrain and cortex. Accordingly, we hypothesize that the dopaminergic-activating effect of cocaine requires stimulation of the dopaminergic neurons by afferents of the ventral tegmental area (VTA). We sought to determine if afferents of the VTA are activated following cocaine administration. Rats were injected in the VTA with retrogradely transported Fluoro-Gold and, after 1 week, were allowed to self-administer cocaine or saline via jugular catheters for 2 h on 6 consecutive days. Other rats received a similar amount of investigator- administered cocaine through jugular catheters. Afterward, the rats were killed and the brains processed immunohistochemically for retrogradely transported tracer and Fos, the protein product of the neuronal activation-associated immediate early gene, c-fos. Forebrain neurons exhibiting both Fos and tracer immunoreactivity were enriched in both cocaine groups relative to the controls only in the globus pallidus and ventral pallidum, which, together, represented a minor part of total forebrain retrogradely labeled neurons.
    [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]
  • Circuit Architecture of VTA Dopamine Neurons Revealed by Systematic Input-Output Mapping
    Article Circuit Architecture of VTA Dopamine Neurons Revealed by Systematic Input-Output Mapping Graphical Abstract Authors Kevin T. Beier, Elizabeth E. Steinberg, Katherine E. DeLoach, ..., Eric J. Kremer, Robert C. Malenka, Liqun Luo Correspondence [email protected] (R.C.M.), [email protected] (L.L.) In Brief A combination of state-of-the-art viral- genetic tools shows that dopaminergic neurons in the ventral tegmental area (VTA-DA) employ biased-input/discrete- output circuit architecture, allowing the construction of an input-output map for further investigation of the neural circuits underlying the different functions of these neurons in psychological processes and brain diseases. Highlights d VTA dopamine (DA) and GABA neurons receive similar inputs from diverse sources d VTA-DA neurons projecting to different output sites receive biased input d VTA-DA neurons projecting to lateral and medial NAc innervate non-overlapping targets d A top-down anterior cortex/VTA-DA/lateral NAc circuit is reinforcing Beier et al., 2015, Cell 162, 622–634 July 30, 2015 ª2015 Elsevier Inc. http://dx.doi.org/10.1016/j.cell.2015.07.015 Article Circuit Architecture of VTA Dopamine Neurons Revealed by Systematic Input-Output Mapping Kevin T. Beier,1,2 Elizabeth E. Steinberg,2 Katherine E. DeLoach,1 Stanley Xie,1 Kazunari Miyamichi,1,5 Lindsay Schwarz,1 Xiaojing J. Gao,1,6 Eric J. Kremer,3,4 Robert C. Malenka,2,* and Liqun Luo1,* 1Howard Hughes Medical Institute and Department of Biology, Stanford University, Stanford, CA 94305, USA 2Nancy Pritzker Laboratory,
    [Show full text]
  • Using High-Resolution MR Imaging at 7T to Evaluate the Anatomy of the Midbrain ORIGINAL RESEARCH Dopaminergic System
    Using High-Resolution MR Imaging at 7T to Evaluate the Anatomy of the Midbrain ORIGINAL RESEARCH Dopaminergic System M. Eapen BACKGROUND AND PURPOSE: Dysfunction of DA neurotransmission from the SN and VTA has been D.H. Zald implicated in neuropsychiatric diseases, including Parkinson disease and schizophrenia. Unfortunately, these midbrain DA structures are difficult to define on clinical MR imaging. To more precisely evaluate J.C. Gatenby the anatomic architecture of the DA midbrain, we scanned healthy participants with a 7T MR imaging Z. Ding system. Here we contrast the performance of high-resolution T2- and T2*-weighted GRASE and FFE J.C. Gore MR imaging scans at 7T. MATERIALS AND METHODS: Ten healthy participants were scanned by using GRASE and FFE se- quences. CNRs were calculated among the SN, VTA, and RN, and their volumes were estimated by using a segmentation algorithm. RESULTS: Both GRASE and FFE scans revealed visible contrast between midbrain DA regions. The GRASE scan showed higher CNRs compared with the FFE scan. The T2* contrast of the FFE scan further delineated substructures and microvasculature within the midbrain SN and RN. Segmentation and volume estimation of the midbrain SN, RN, and VTA showed individual differences in the size and volume of these structures across participants. CONCLUSIONS: Both GRASE and FFE provide sufficient CNR to evaluate the anatomy of the midbrain DA system. The FFE in particular reveals vascular details and substructure information within the midbrain regions that could be useful for examining
    [Show full text]
  • Ventral Tegmental Area Glutamate Neurons: Electrophysiological Properties and Projections
    15076 • The Journal of Neuroscience, October 24, 2012 • 32(43):15076–15085 Cellular/Molecular Ventral Tegmental Area Glutamate Neurons: Electrophysiological Properties and Projections Thomas S. Hnasko,1,2,3,4 Gregory O. Hjelmstad,2,3 Howard L. Fields,2,3 and Robert H. Edwards1,2 Departments of 1Physiology and 2Neurology, University of California San Francisco, San Francisco, California 94143, 3Ernest Gallo Clinic and Research Center, Emeryville, California 94608, and 4Department of Neurosciences, University of California San Diego, La Jolla, California 92093 The ventral tegmental area (VTA) has a central role in the neural processes that underlie motivation and behavioral reinforcement. Although thought to contain only dopamine and GABA neurons, the VTA also includes a recently discovered population of glutamate neurons identified through the expression of the vesicular glutamate transporter VGLUT2. A subset of VGLUT2 ϩ VTA neurons corelease dopamine with glutamate at terminals in the NAc, but others do not express dopaminergic markers and remain poorly characterized. Using transgenic mice that express fluorescent proteins in distinct cell populations, we now find that both dopamine and glutamate neurons in the medial VTA exhibit a smaller hyperpolarization-activated current (Ih ) than more lateral dopamine neurons and less ϩ consistent inhibition by dopamine D2 receptor agonists. In addition, VGLUT2 VTA neurons project to the nucleus accumbens (NAc), lateral habenula, ventral pallidum (VP), and amygdala. Optical stimulation of VGLUT2 ϩ projections expressing channelrhodopsin-2 further reveals functional excitatory synapses in the VP as well as the NAc. Thus, glutamate neurons form a physiologically and anatom- ically distinct subpopulation of VTA projection neurons. Introduction well as to the amygdala, septum, hippocampus, and prefrontal Dopamine neurons of the ventral midbrain are classically divided cortex (PFC) (Fields et al., 2007; Ikemoto, 2007).
    [Show full text]
  • The Nuclear Pattern of the Nok-Tectal Portions of the Midbrain and Isthmus in the Opossum
    THE NUCLEAR PATTERN OF THE NOK-TECTAL PORTIONS OF THE MIDBRAIN AND ISTHMUS IN THE OPOSSUM RUSSELL T. WOODBURNE Department of Anatomy, Uniwersity of Yichigan SIX PLATES (TWELVE FIGURES) INTRODUCTION It is logical that the present series of descriptions of the nuclear pattern of the midbrain tegmentum in mammals should begin with the account of this region in marsupials, since the American opossum presents a simplified and generalized type of mammalian midbrain. The material employed in the present study consists of toluidin blue series, cut in various planes, of the brain of the American opossum, Didelphis virginiana. These preparations are a part of the Huber Neurological Collection of the Department of Anatomy of the University of Michigan. The literature particularly pertinent to specific nuclear de- scriptions will be discussed in connection with such descrip- tions and the general literature dealing with other than marsupial forms is dealt with in other sections of this series of papers and complete reference made in the comprehensive bibliography. There are, however, certain papers of which some mention should be made. The series of papers by Castaldi ('23, '24, '26) gave the basis for the nomenclature and the general pattern of subdivision followed here. Tsai's ('25) account of portions of the marsupial midbrain, although con- cerned primarily with tectal and pretectal areas, gave some aid in orientation. Certain of the pretectal regions were con- sidered in the light of earlier accounts of Chu ( '32) and Bodian ('40). The text of Ariens Kappers, Huber and Crosby ('36) was used for general orientation and comparative information.
    [Show full text]
  • Neurons in the Ventral Tegmentum Have Separate Populations
    332 Brain Research, 321 (1984) 332-336 Elsevicr BRE 20426 Neurons in the ventral tegmentum have separate populations projecting to telencephalon and inferior olive, are histochemically different, and may receive direct visual input JAMES H. FALLON, LAURENCE C. SCHMUED, CHARLES WANG, ROSS MILLER and GERALD BANALES Department of Anatomy, University of California, lrvine, CA 92 717 (U.S.A.) (Accepted June 5th, 1984) Key words: visual system -- basal ganglia -- prefrontal cortex -- inferior olive -- ventral tegmental area -- dopamine The connections of the ventral tegmental area (VTA) and medial terminal nucleus (MTN) of the accessory optic system were stud- ied in the albino rat. Using injection of two fluorescent retrograde tracers it was found that individual neurons of the VTA project to frontal cortices or the inferior olive but not both structures. Using combined retrograde fluorescent tracers and glyoxylic acid histo- chemistry, it was found that although a third of the cells projecting to frontal cortex contained catecholamine, none of the cells projecting to the inferior olive contained catecholamine. Thus, these portions of the ascending and descending VTA systems are inde- pendent. In addition, using injections of the anterograde transneuronal tracer [3H]adenosine into one eye, it was found that cells in the VTA, as well as the MTN, contained the tracer. Therefore, there is a basis for direct retino-mesentelencephalicpathways through the VTA. The ventral tegmental area (VTA) is a functionally to the ipsilateral flocculus 3, which then projects to and anatomically diverse region of the midbrain. The the ipsilateral vestibular nuclei 15,25,27. The vestibular VTA contains both dopaminergic (A10 cell group) nuclei affect eye movements via projections to crani- and non-dopaminergic neurons that project to telen- al nuclei III, IV and VI.
    [Show full text]
  • Forebrain Origins and Terminations of the Medial Forebrain Bundle Metabolically Activated by Rewarding Stimulation Or by Reward- Blocking Doses of Pimozide’
    0270.6474/85/0505-1246$02.00/O The Journal of Neuroscience Copyright 0 Society for Neuroscience Vol. 5, No. 5, pp. 1246-1261 Printed in U.S.A. May 1985 Forebrain Origins and Terminations of the Medial Forebrain Bundle Metabolically Activated by Rewarding Stimulation or by Reward- blocking Doses of Pimozide’ C. R. GALLISTEL,* Y. GOMITA,3 ELNA YADIN,4 AND KENNETH A. CAMPBELL5 Department of Psychology, University of Pennsylvania, Philadelphia, Pennsylvania 19104 Abstract iological investigation as a likely substrate for the rewarding effect of MFB stimulation. They also suggest that dopami- Using [14C]-2-deoxyglucose autoradiography, we deter- nergic projection systems may not form part of the reward mined which forebrain and diencephalic areas showed met- pathway itself. abolic alterations in response to unilateral electrical stimu- lation of the posterior medial forebrain bundle at parameters Behavioral experiments, using methods for determining quantita- chosen to produce a just-submaximal rewarding effect. At tive properties of the neural substrate, have led to the conclusion these parameters, only a few areas were activated. There that the directly stimulated substrate for electrical self-stimulation of was no detectable activation anterior or dorsal to the genu the medial forebrain bundle (MFB) is comprised in substantial part of the corpus callosum. Just anterior to the anterior commis- of long, thin myelinated axons descending from forebrain nuclei to sure, there was strong activation of the vertical limb of the the anterior ventral tegmentum (C. Bielajew and P. Shizgal, manu- diagonal band of Broca, with a focus in the nucleus of the script submitted for publication; Gallistel et al., 1981).
    [Show full text]
  • Modeling Uncertainty-Seeking Behavior Mediated by Cholinergic Influence on Dopamine
    bioRxiv preprint doi: https://doi.org/10.1101/699595; this version posted July 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. Modeling Uncertainty-Seeking Behavior Mediated by Cholinergic Influence on Dopamine Marwen Belkaid1,2,* and Jeffrey L. Krichmar3,4 Abstract 1 Introduction Recent findings suggest that acetylcholine me- Animals constantly face uncertainty due to diates uncertainty-seeking behaviors through noisy and incomplete information about the its projection to dopamine neurons – another environment. From the information-processing neuromodulatory system known for its major perspective, uncertainty is typically considered implication in reinforcement learning and a burden, an issue that has to be resolved decision-making. In this paper, we propose a for the animal to behave correctly [Cohen leaky-integrate-and-fire model of this mecha- et al., 2007; Rao, 2010]. In the framework of nism. It implements a softmax-like selection reinforcement learning, for example, to allow with an uncertainty bonus by a cholinergic optimal exploitation and outcome maximiza- drive to dopaminergic neurons, which in turn tion, agents must explore the environment influence synaptic currents of downstream and gather information about action–outcome neurons. The model is able to reproduce contingencies [Sutton and Barto, 1998; Rao, experimental data in two decision-making 2010]. tasks. It also predicts that i) in the absence The neural mechanisms driving the decision of cholinergic input, dopaminergic activity to perform actions with uncertain outcomes would not correlate with uncertainty, and that are still poorly understood.
    [Show full text]
  • Anatomy, Pigmentation, Ventral and Dorsal Subpopulations of the Substantia Nigra, and Differential Cell Death in Parkinson's Disease 389
    388 Journal ofNeurology, Neurosurgery, and Psychiatry 1991;54:388-396 Anatomy, pigmentation, ventral and dorsal J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.54.5.388 on 1 May 1991. Downloaded from subpopulations of the substantia nigra, and differential cell death in Parkinson's disease W R G Gibb, A J Lees Abstract median 75 years), six cases of PD (aged 61-87 In six control subjects pars compacta years, median 69 years), and 13 persons with- nerve cells in the ventrolateral substan- out PD but with Lewy bodies in the SN, tia nigra had a lower melanin content known as incidental Lewy body disease or than nerve cells in the dorsomedial presymptomatic PD3 (aged 50-87 years, region. This coincides with a natural median 77 years) were examined. The anatomical division into ventral and incidental cases showed Lewy bodies and mild dorsal tiers, which represent function- nerve cell loss in the SN pars compacta, as ally distinct populations. In six cases of well as in the locus coeruleus. They showed Parkinson's disease (PD) the ventral tier more severe nigral cell degeneration than is showed very few surviving nerve cells normal for ageing, nigral cell loss intermediate compared with preservation of cells in between normal and PD, and neuronal the dorsal tier. In 13 subjects without inclusions (Lewy bodies and pale bodies) PD, but with nigral Lewy bodies and cell identical to those of PD. Dopamine depletion loss, the degenerative process started in is known to be present at the time of onset of the ventral tier, and spread to the dorsal PD, and such cases were presumed to tier.
    [Show full text]
  • The Pons Neurological System > Brainstem & Cranial Nerve Anatomy > Brainstem & Cranial Nerve Anatomy
    The Pons Neurological System > Brainstem & Cranial Nerve Anatomy > Brainstem & Cranial Nerve Anatomy THE PONS OVERVIEW Here, we'll learn about the pons. • Start a table. • Denote that, from a clinician's perspective, the pons is, most notably, the neurobiological site of injury that produces locked-in syndrome. • Start a mid-sagittal section. First, draw the different brainstem levels, from superior to inferior: • Midbrain • Pons • Medulla KEY SURROUNDING STRUCTRES Label the anterior/posterior orientational plane of our diagram. • Include the key structures that border the brainstem: • The hyopthalamus, superiorly. • The cerebellum, posteriorly. • The cervical spinal cord, inferiorly. • And the temporal lobe, laterally. • Now, point out the pontine basis, which comprises pontine nuclei and pontocerebellar fiber tracts. • Shade in the CSF and indicate that the 4th ventricle lies at the level of the pons. RADIOGRAPHIC AXIAL SECTION • Before we draw a detailed anatomical section, let's review an axial section in radiographic perspective, which is the 1 / 4 common clinical perspective. • Show its anterior/posterior orientational plane. • Draw the pons. • Demarcate the pontine basis, anteriorly. • In this view, show its representative pontine nuclei. • And show its pontocerebellar fibers, which cross the pons and pass into the middle cerebellar peduncle as an important step in the corticopontocerebellar pathway. Clinical Correlation: central pontine myelinolysis ANATOMIC AXIAL SECTION Now, let's draw an anatomic axial outline of the pons. • Indicate the anterior–posterior axis of our diagram. • Label the left side of the page as nuclei and the right side as tracts. • Then, label the fourth ventricle — the cerebrospinal fluid space of the pons. • Next, distinguish the large basis from the comparatively small tegmentum.
    [Show full text]
  • The Role of Glutamate and Its Receptors in Mesocorticolimbic Dopaminergic Regions in Opioid Addiction
    University of Nebraska - Lincoln DigitalCommons@University of Nebraska - Lincoln Public Health Resources Public Health Resources 2009 The role of glutamate and its receptors in mesocorticolimbic dopaminergic regions in opioid addiction Yuan Guo Xi’an Jiaotong University School of Medicine Hui-Ling Wang Xi’an Jiaotong University School of Medicine Xiao-Hui Xiang Medical College of Chinese People’s Armed Police Forces Yan Zhao Xi’an Jiaotong University School of Medicine Follow this and additional works at: https://digitalcommons.unl.edu/publichealthresources Part of the Public Health Commons Guo, Yuan; Wang, Hui-Ling; Xiang, Xiao-Hui; and Zhao, Yan, "The role of glutamate and its receptors in mesocorticolimbic dopaminergic regions in opioid addiction" (2009). Public Health Resources. 106. https://digitalcommons.unl.edu/publichealthresources/106 This Article is brought to you for free and open access by the Public Health Resources at DigitalCommons@University of Nebraska - Lincoln. It has been accepted for inclusion in Public Health Resources by an authorized administrator of DigitalCommons@University of Nebraska - Lincoln. Neuroscience and Biobehavioral Reviews 33 (2009) 864–873 Contents lists available at ScienceDirect Neuroscience and Biobehavioral Reviews journal homepage: www.elsevier.com/locate/neubiorev Review The role of glutamate and its receptors in mesocorticolimbic dopaminergic regions in opioid addiction Yuan Guo a, Hui-Ling Wang a,b, Xiao-Hui Xiang c, Yan Zhao a,* a Department of Physiology and Pathophysiology, Xi’an Jiaotong
    [Show full text]