DOCSLIB.ORG

Effect of Bilateral 6-Hydroxydopamine Lesions of the Medial Forebrain Bundle on Reaction Time A.D

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Effect of Bilateral 6-Hydroxydopamine Lesions of the Medial Forebrain Bundle on Reaction Time A.D Effect of Bilateral 6-Hydroxydopamine Lesions of the Medial Forebrain Bundle on Reaction Time A.D. Smith, Ph.D., M. Amalric, Ph.D., G.F. Koob, Ph.D., and M.J. Zigmond, Ph.D. Overt symptoms of Parkinson’s disease do not manifest week testing period and akinetic deficits expressed by an themselves until there is a substantial loss of the increase in delayed responding. In addition, larger DA dopaminergic nigrostriatal projection. However, as depletions (у95%) profoundly altered motor control with neuroprotective strategies are developed, it will be essential decreases in percent correct responses, increases in delayed to detect the disease in its preclinical phase. Performance on responses and increases in reaction time. These results conditioned reaction time tasks is known to be impaired by suggest that reaction time may be a relatively sensitive extensive 6-hydroxydopamine-induced lesions of the measure of preclinical or subtle deficits, although it might nigrostriatal dopamine pathway. However, the effect of be even more useful in quantitating the severity of depletion smaller lesions on a reaction time task has not been once overt deficits or symptoms appear and has the systematically assessed. We, therefore, used this test to advantage of measuring such deficits over time to follow examine behavioral deficits as a function of striatal recovery of function. Furthermore since reaction time dopamine loss. When injected at doses that produced deficits required extensive loss of dopamine, these results striatal DA depletion Ͻ50%, 6-hydroxydopamine infused are consistent with a predominant role of extrasynaptic in the medial forebrain bundle produced no reliable dopamine in the mediation of relatively skilled motor tasks. impairment in the reaction time task. Higher doses [Neuropsychopharmacology 26:756–764, 2002] producing у60% DA depletion in the striatum produced a © 2002 American College of Neuropsychopharmacology. decrease in the percent correct responding throughout the 5 Published by Elsevier Science Inc. KEY WORDS: Reaction time; 6-Hydroxydopamine; Striatum; The primary neuropathology of Parkinson’s disease is Parkinson’s disease; Medial forebrain bundle; Dopamine the loss of dopamine (DA) neurons within the substan- tia nigra (SN) and massive depletion of DA in the stria- tum, the terminal region of the SN. This loss of DA ap- From the Department of Neurology, University of Pittsburgh pears to be responsible for the most prominent symptoms (ADS, MJZ), Department of Neuropharmacology, The Scripps of Parkinson’s disease. The degree of neurological deficit Research Institute (ADS, GFK), and Laboratoire de Neurobiologie Cellulaire et Fonctionnelle, Laboratoire associe à l’University Aix- is related to the loss of striatal DA (Hornykiewicz Marseille II CNRS (MA). and Kish 1987). The neurotoxins 6-hydroxydopamine Address correspondence to: Amanda D. Smith, Ph.D., Depart- (6-OHDA) and 1-methyl-4-phenyl-1,2,3,6-tetrahydro- ment of Neurology, S-510 Biomedical Science Tower, Pittsburgh, PA 15213, Tel.: (412) 383-7604, fax: (412) 624-7327, E-mail: smithad@ pyridine (MPTP), used extensively to induce selective pitt.edu loss of DA neurons within the SN, provide animal mod- Received April 5, 2001; revised October 11, 2001; accepted els that share several of the characteristics of Parkin- November 28, 2001. Online publication: 11/29/01 at www.acnp.org/citations/ son’s disease (see reviews by Zigmond and Keefe Npp112901215. 1997; Jenner and Marsden 1986; Gerlach and Riederer NEUROPSYCHOPHARMACOLOGY 2002–VOL. 26, NO. 6 © 2002 American College of Neuropsychopharmacology Published by Elsevier Science Inc. 0893-133X/02/$–see front matter 655 Avenue of the Americas, New York, NY 10010 PII S0893-133X(01)00420-1 NEUROPSYCHOPHARMACOLOGY 2002–VOL. 26, NO. 6 Bilateral 6-OHDA on Reaction Time 757 1996; Przedborski and Jackson-Lewis 1998). In addition, in the number of delayed and premature responses also whereas intrastriatal injection of indirect DA agonists was observed, suggesting a disruption in cognitive as induces stereotypy (Costall et al. 1973; Statton and So- well as motor function. Deficits in the reaction time task lomon 1984), 6-OHDA lesions of the striatum block this following bilateral 6-OHDA lesions appeared after a stereotyped behavior (Price and Fibiger 1974). Finally, 70% depletion of striatal DA, were present one week chronic administration of DA receptor antagonists pro- post-lesion, and persisted for at least three months post- duce extrapyramidal effects reminiscent of Parkinson’s lesion (Moukhles et al. 1994). disease, and this is believed to be due to their action at The effects of smaller lesions have not been system- D2 receptors located in the striatum (Coffin et al. 1989). atically assessed. However, the ability to detect deficits Although resting tremor and muscular rigidity are prior to a majority loss of striatal DA would be quite generally not reported in rodents after pharmacological useful. Recent evidence shows that several trophic fac- manipulation of the nigrostriatal pathway, deficits in tors are neuroprotective in animal models of Parkin- movement initiation and execution have been studied son’s disease when these factors are administered either using several tests including a conditioned reaction before or after appreciable loss of striatal DA and SN time task. In this task, animals are typically required to neurons (Choi-Lundberg et al. 1997, 1998; Rosenblad et respond in a particular way and within a limited period al. 1998; Connor et al. 1999; Kozlowski et al. 2000). in order to receive a reward, such as a food pellet. This Should these or other treatments prove to be clinically behavioral paradigm is responsive to pharmacological efficacious, it will be essential to develop neurological manipulation of dopaminergic neurotransmission me- tests that detect nigrostriatal degeneration in the “pre- diated by the D2 subtype of DA receptors (Amalric and clinical” phase of Parkinson’s disease so that neuropro- Koob 1987, 1989; Amalric et al. 1993, 1995; Smith et al. tective strategies can be used to delay or even prevent 2000). For example, we have shown that low dose the appearance of more disruptive functional deficits. blockade of D2 receptors, but not D1 or D3 receptors, de- Therefore, in the present study the sensitivity of the creased correct responses in the conditioned reaction conditioned reaction time task to striatal DA loss was time task, increased delayed responses, and lengthened examined in 6-OHDA–lesioned rats. reaction time in a manner suggestive of dysfunctions in movement initiation (Amalric et al. 1993; Smith et al. 2000). Moreover, deficits in reaction time have also been reported in Parkinson’s disease (Evarts et al. 1981; MATERIALS AND METHODS Gauntlett-Gilbert and Brown 1998; Berry et al. 1999). Subjects These deficits appear to be mediated by the nigrostri- atal dopaminergic pathway, as 6-OHDA-induced loss Twenty four male Wistar rats (Beckman, The Scripps of SN neurons and striatal DA, and not accumbal DA, Research Institute, La Jolla, CA), weighing 120–150 g at produces impairments in this task (Amalric and Koob the start of the experiment, were housed in groups of 1987), and intrastriatal infusion of the DA receptor an- three and maintained on a reverse 12-h light/dark cycle tagonist haloperidol has a comparable effect (Amalric with lights on at 10 P.M. Behavioral measurements were and Koob 1989). conducted during the animals’ light cycle between the Previous experiments have examined the effect of hours of 7 and 10 A.M., 5 days a week. Rats were initially large 6-OHDA-induced lesions on performance in a food deprived for 24 h at the start of training and subse- simple and choice reaction time task. Because of the de- quently food restricted to 15–17 g of food (Harlan Tek- bilitating effects of bilateral lesions, the majority of lad Laboratories, Bartonville, IL) per day for the dura- these studies examined the effect of unilateral lesions tion of the experiment to maintain them at 80–85% of on performance in the reaction time task. Massive uni- their free food body weight. Water was freely available lateral lesions of the nigrostriatal pathway (у95% loss throughout the experiment. All procedures were in of striatal DA) produced unilateral deficits in move- strict accordance with the guidelines for the NIH Care ment initiation, which had not recovered two months and Use of Laboratory Animals and approved by the later. The deficits were characterized by an increase in Institutional Animal Care and Use Committee of The the reaction time on the side contralateral to the lesion Scripps Research Institute. and a preferential response bias ipsilateral to the lesion (Carli et al. 1985, 1989; Brown and Robbins 1989, 1991; Training Procedure Phillips and Brown 1999). In the few cases in which bi- lateral lesions of the nigrostriatal pathway have been Experiments were conducted in standard experimental examined, profound deficits in the reaction time task chambers (29 cm l ϫ 24 cm w ϫ 19.5 cm h; Coulbourn were observed, and included lengthened reaction times Instruments, Allentown, PA) placed in sound attenu- and decreases in the percent correct responses (Amalric ated cubicles. A retractable lever (BRS/LVE), located 4 and Koob 1987, 1989; Moukhles et al. 1994). An increase cm above the grid floor and 9 cm below the cue light 758 A.D. Smith et al. NEUROPSYCHOPHARMACOLOGY 2002–VOL. 26, NO. 6 (0.5 cm diameter), was extended immediately after the days. During the recovery period, two rats that had re- animals were placed in the experimental chambers. Af- ceived 4 ␮g 6-OHDA had to be fed by oral gavage. ter completion of a successful trial, the food pellet was These rats received 3 ml of Sustacal supplemented with delivered to the food trough in less than 1 s. The tempo- 2 g of sucrose by oral gavage 3 times a day, and had free ral resolution of the instrumental setup was 10 msec.
Load more

Recommended publications
  • 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.
    [Show full text]
  • The Effects of Habenular and Medial Forebrain Bundle Lesions on Sexual Behavior in Female Rats'
    The effects of habenular and medial forebrain bundle lesions on sexual behavior in female rats' CHARLES H. RODGERS:?, DEPARTMENT OF PHYSIOLOGY, STANFORD UNIVERSITY O. THOMAS LAW, DEPARTMENT OF PSYCHOLOGY, CLAREMONT GRADUATE SCHOOL A comparison was made of the effects of habenular and subsequent to the experiencing trials, the preoperative medial forebrain bundle lesions on female rat sexual behavior tests were initiated. Each S received one 15 min. trial as measured by the lordosis-to-mount ratio, and by the fe­ while nonreceptive and one 15 min. trial while receptive. male's avoidance of sexual contact. Results show that Receptivity was induced as described above. destruction of the habenulae causes a decreased lordosis Lesions were produced by monopolar stainless steel response, and a greater avoidance of male sexual contacts. electrodes, insulated except for .008 in. at the tip, under Medial forebrain bundle lesions had a less pronounced effect the following conditions: (1) Habenula (Hab)-2 rnA on the female's behavior. anodal current for 10 sec.; (2) Medial forebrain bundle (MFB)-2 rnA anodal current for 15 sec. Coordinates Few studies have reported the effects of subcortical for the target areas were obtained fromdeGroot(1959). destruction on copulatory behavior in the female rat. Copulatory tests were conducted in a cylindrical It is accepted that circumscribed destruction of the mating arena made of clear Plexiglas 18 in. high x anterior hypothalamus causes female rats to become 20 in. in diameter, supported on a table surfaced with anovulatory and behaviorally nonreceptive (Flerko, 1/2-in. hardware cloth. A mirror, fixed at an angle 1963).
    [Show full text]
  • Afferent Connections to the Striatum and the Nucleus Accumbens
    THE JOURNAL OF COMPARATIVE NEUROLOGY 378:16–49 (1997) Basal Ganglia Organization in Amphibians: Afferent Connections to the Striatum and the Nucleus Accumbens OSCAR MARI´N,1 AGUSTI´N GONZA´ LEZ,1* AND WILHELMUS J.A.J. SMEETS2 1Departamento de Biologı´a Celular, Facultad de Biologı´a, Universidad Complutense, Madrid, Spain 2 Graduate School of Neurosciences of Amsterdam, Research Institute of Neurosciences and Department of Anatomy and Embryology, Vrije Universiteit, Amsterdam, The Netherlands ABSTRACT As part of a research program to determine if the organization of basal ganglia (BG) of amphibians is homologous to that of amniotes, the afferent connections of the BG in the anurans Xenopus laevis and Rana perezi and the urodele Pleurodeles waltl were investigated with sensitive tract-tracing techniques. Hodological evidence is presented that supports a division of the amphibian BG into a nucleus accumbens and a striatum. Both structures have inputs in common from the olfactory bulb, medial pallium, striatopallial transition area, preoptic area, ventral thalamus, ventral hypothalamic nucleus, posterior tubercle, several mesencephalic and rhombencephalic reticular nuclei, locus coeruleus, raphe, and the nucleus of the solitary tract. Several nuclei that project to both subdivisions of the BG, however, show a clear preference for either the striatum (lateral amygdala, parabrachial nucleus) or the nucleus accumbens (medial amygdala, ventral midbrain tegmentum). In addition, the anterior entopeduncular nucleus, central thalamic nucleus, anterior and posteroventral divisions of the lateral thalamic nucleus, and torus semicircularis project exclusively to the striatum, whereas the anterior thalamic nucleus, anteroventral, and anterodorsal tegmental nuclei provide inputs solely to the nucleus accumbens. Apart from this subdivision of the basal forebrain, the results of the present study have revealed more elaborate patterns of afferent projections to the BG of amphibians than previously thought.
    [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]
  • Hedonic Tone Is Associated with Left Supero-Lateral Medial Forebrain Bundle Microstructure
    Psychological Medicine (2015), 45, 865–874. © Cambridge University Press 2014 ORIGINAL ARTICLE doi:10.1017/S0033291714001949 Hedonic tone is associated with left supero-lateral medial forebrain bundle microstructure T. Bracht1,2*, A. N. Doidge1,2, P. A. Keedwell2 and D. K. Jones1,2 1 Cardiff University Brain Research Imaging Centre (CUBRIC), School of Psychology, Cardiff University, Cardiff, UK 2 Neuroscience, Mental Health Research Institute, Cardiff University, Cardiff, UK Background. The medial forebrain bundle (MFB) is an important pathway of the reward system. Two branches have been described using diffusion magnetic resonance imaging (MRI)-based tractography: the infero-medial MFB (imMFB) and the supero-lateral MFB (slMFB). Previous studies point to white-matter microstructural alterations of the slMFB in major depressive disorder (MDD) during acute episodes. To extend this finding, this study investigates whether white-matter microstructure is also altered in MDD patients that are in remission. Further, we explore associa- tions between diffusion MRI-based metrics of white-matter microstructure of imMFB, slMFB and hedonic tone, the abil- ity to derive pleasure. Method. Eighteen remitted depressed (RD) and 22 never depressed (ND) participants underwent high angular resol- ution diffusion-weighted imaging (HARDI) scans. To reconstruct the two pathways of the MFB (imMFB and slMFB) we used the damped Richardson–Lucy (dRL) algorithm. Mean fractional anisotropy (FA) was sampled along the tracts. Results. Mean FA of imMFB, slMFB and a comparison tract (the middle cerebellar peduncle) did not differ between ND and RD participants. Hedonic capacity correlated negatively with mean FA of the left slMFB, explaining 21% of the variance. Conclusions.
    [Show full text]
  • The Habenular Nuclei: a Conserved Asymmetric Relay Station in the Vertebrate Brain
    The habenular nuclei: a conserved asymmetric relay station in the vertebrate brain The Harvard community has made this article openly available. Please share how this access benefits you. Your story matters Citation Bianco, Isaac H. and Stephen W. Wilson. 2009. The habenular nuclei: a conserved asymmetric relay station in the vertebrate brain. Philosophical Transactions of the Royal Society B: Biological Sciences 364(1519): 1005-1020. Published Version doi://10.1098/rstb.2008.0213 Citable link http://nrs.harvard.edu/urn-3:HUL.InstRepos:10886852 Terms of Use This article was downloaded from Harvard University’s DASH repository, and is made available under the terms and conditions applicable to Other Posted Material, as set forth at http:// nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of- use#LAA Phil. Trans. R. Soc. B (2009) 364, 1005–1020 doi:10.1098/rstb.2008.0213 Published online 4 December 2008 Review The habenular nuclei: a conserved asymmetric relay station in the vertebrate brain Isaac H. Bianco1,2,* and Stephen W. Wilson1,* 1Department of Cell and Developmental Biology, University College London, London WC1E 6BT, UK 2Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA The dorsal diencephalon, or epithalamus, contains the bilaterally paired habenular nuclei and the pineal complex. The habenulae form part of the dorsal diencephalic conduction (DDC) system, a highly conserved pathway found in all vertebrates. In this review, we shall describe the neuroanatomy of the DDC, consider its physiology and behavioural involvement, and discuss examples of neural asymmetries within both habenular circuitry and the pineal complex.
    [Show full text]
  • Neuroimaging Advances in Deep Brain Stimulation: Review of Indications, Anatomy, and Brain Connectomics
    REVIEW ARTICLE Neuroimaging Advances in Deep Brain Stimulation: Review of Indications, Anatomy, and Brain Connectomics E.H. Middlebrooks, R.A. Domingo, T. Vivas-Buitrago, L. Okromelidze, T. Tsuboi, J.K. Wong, R.S. Eisinger, L. Almeida, M.R. Burns, A. Horn, R.J. Uitti, R.E. Wharen Jr, V.M. Holanda, and S.S. Grewal ABSTRACT SUMMARY: Deep brain stimulation is an established therapy for multiple brain disorders, with rapidly expanding potential indi- cations. Neuroimaging has advanced the field of deep brain stimulation through improvements in delineation of anatomy, and, more recently, application of brain connectomics. Older lesion-derived, localizationist theories of these conditions have evolved to newer, network-based “circuitopathies,” aided by the ability to directly assess these brain circuits in vivo through the use of advanced neuroimaging techniques, such as diffusion tractography and fMRI. In this review, we use a combination of ultra-high-field MR imaging and diffusion tractography to highlight relevant anatomy for the currently approved indications for deep brain stimulation in the United States: essential tremor, Parkinson disease, drug-resistant epilepsy, dystonia, and obsessive-compulsive disorder. We also review the literature regarding the use of fMRI and diffusion tractography in under- standing the role of deep brain stimulation in these disorders, as well as their potential use in both surgical targeting and de- vice programming. ABBREVIATIONS: AL ¼ ansa lenticularis; ALIC ¼ anterior limb of the internal capsule; ANT ¼
    [Show full text]
  • Frontal White Matter Architecture Predicts Efficacy of Deep Brain
    Coenen et al. Translational Psychiatry (2019) 9:197 https://doi.org/10.1038/s41398-019-0540-4 Translational Psychiatry ARTICLE Open Access Frontal white matter architecture predicts efficacy of deep brain stimulation in major depression Volker A. Coenen 1,2,3,4,5,ThomasE.Schlaepfer 2,4,6,7, Bettina Bewernick7,8, Hannah Kilian2,6, Christoph P. Kaller2,4,9, Horst Urbach2,9,10,MengLi1,2,11 and Marco Reisert1,2 Abstract Major depression is a frequent and severe disorder, with a combination of psycho- and pharmacotherapy most patients can be treated. However, ~20% of all patients suffering from major depressive disorder remain treatment resistant; a subgroup might be treated with deep brain stimulation (DBS). We present two trials of DBS to the superolateral medial forebrain bundle (slMFB DBS; FORESEE I and II). The goal was to identify informed features that allow to predict treatment response. Data from N = 24 patients were analyzed. Preoperative imaging including anatomical sequences (T1 and T2) and diffusion tensor imaging (DTI) magnetic resonance imaging sequences were used together with postoperative helical CT scans (for DBS electrode position). Pathway activation modeling (PAM) as well as preoperative structural imaging and morphometry was used to understand the response behavior of patients (MADRS). A left fronto-polar and partly orbitofrontal region was identified that showed increased volume in preoperative anatomical scans. Further statistical analysis shows that the volume of this “HUB-region” is predictive for later MADRS response from DBS. The HUB region connects to typical fiber pathways that have been addressed before 1234567890():,; 1234567890():,; 1234567890():,; 1234567890():,; in therapeutic DBS in major depression.
    [Show full text]
  • Download English-US Transcript (PDF)
    MITOCW | MIT9_14S14_lec12.mp3 The following content is provided under a Creative Commons license. Your support will help MIT OpenCourseWare continue to offer high-quality educational resources for free. To make a donation or view additional materials from hundreds of MIT courses, visit MIT OpenCourseWare at [email protected]. PROFESSOR: All right. Listen, I didn't much like the way things went in the last class. And the reason, it's because of the way I had planned it. By having a quiz not on the chapter we're covering in a day, you're always going to spend your time reviewing for the quiz, and you're not going to read-- or at least, you won't all read the chapter for today. So it's not a very good way to do it. I asked you to read chapter 12, I believe, for today. You all should do that if you want to get the maximum out of the class. So this is what I would like to change. There's a number-- I talked to some of the students, and I talked to Caitlin. I would like to have a quiz every class, but only one, occasionally two questions. One idea would be to have one fairly easy question on the new chapter, just to make sure you've read it and get you to read it. But I also could have a question on the previous class that you should be able to answer if you've come to the class and gone over the slides afterwards that I post online.
    [Show full text]
  • The Habenular Nuclei: a Conserved Asymmetric Relay Station in the Vertebrate Brain
    The habenular nuclei: a conserved asymmetric relay station in the vertebrate brain The Harvard community has made this article openly available. Please share how this access benefits you. Your story matters Citation Bianco, Isaac H. and Stephen W. Wilson. 2009. The habenular nuclei: a conserved asymmetric relay station in the vertebrate brain. Philosophical Transactions of the Royal Society B: Biological Sciences 364(1519): 1005-1020. Published Version doi://10.1098/rstb.2008.0213 Citable link http://nrs.harvard.edu/urn-3:HUL.InstRepos:10886852 Terms of Use This article was downloaded from Harvard University’s DASH repository, and is made available under the terms and conditions applicable to Other Posted Material, as set forth at http:// nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of- use#LAA Phil. Trans. R. Soc. B (2009) 364, 1005–1020 doi:10.1098/rstb.2008.0213 Published online 4 December 2008 Review The habenular nuclei: a conserved asymmetric relay station in the vertebrate brain Isaac H. Bianco1,2,* and Stephen W. Wilson1,* 1Department of Cell and Developmental Biology, University College London, London WC1E 6BT, UK 2Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA The dorsal diencephalon, or epithalamus, contains the bilaterally paired habenular nuclei and the pineal complex. The habenulae form part of the dorsal diencephalic conduction (DDC) system, a highly conserved pathway found in all vertebrates. In this review, we shall describe the neuroanatomy of the DDC, consider its physiology and behavioural involvement, and discuss examples of neural asymmetries within both habenular circuitry and the pineal complex.
    [Show full text]
  • The Dorsal Diencephalic Conduction System in Reward Processing: Spotlight on the Anatomy and Functions of the Habenular Complex
    Behavioural Brain Research 348 (2018) 115–126 Contents lists available at ScienceDirect Behavioural Brain Research journal homepage: www.elsevier.com/locate/bbr The dorsal diencephalic conduction system in reward processing: Spotlight T on the anatomy and functions of the habenular complex Marc Fakhoury Department of Neurosciences, Faculty of Medicine, Université de Montréal, Montreal, Quebec, H3C3J7, Canada ARTICLE INFO ABSTRACT Keywords: The dorsal diencephalic conduction system (DDC) is a highly conserved pathway in vertebrates that provides a Aversion route for the neural information to flow from forebrain to midbrain structures. It contains the bilaterally paired Dopamine habenular nuclei along with two fiber tracts, the stria medullaris and the fasciculus retroflexus. The habenula is Dorsal diencephalic conduction system the principal player in mediating the dialogue between forebrain and midbrain regions, and functional ab- Habenula normalities in this structure have often been attributed to pathologies like mood disorders and substance use Reward disorder. Following Matsumoto and Hikosaka seminal work on the lateral habenula as a source of negative Serotonin reward signals, the last decade has witnessed a great surge of interest in the role of the DDC in reward-related processes. However, despite significant progress in research, much work remains to unfold the behavioral functions of this intriguing, yet complex, pathway. This review describes the current state of knowledge on the DDC with respect to its anatomy, connectivity, and functions in reward and aversion processes. 1. Introduction the habenula, and the fasciculus retroflexus (FR). It constitutes a rostro- caudal conduction system that merges with the MFB at its rostral and The discovery by Olds and Milner that electrical stimulation of caudal poles.
    [Show full text]
  • [D-Ala2]Deltorphin I-Like Immunoreactivity in the Adult Rat Brain
    Proc. Natl. Acad. Sci. USA Vol. 90, pp. 9635-9639, October 1993 Pharmacology [D-Ala2]Deltorphin I-like immunoreactivity in the adult rat brain: Immunohistochemical localization (amphibian skin peptides/&opioid receptors/dopamine/calbindin) IKUO TOOYAMA*, HIROMICHI ABE*t, TINDARO RENDAt, VITTORIO ERSPAMER§, AND HIROSHI KIMURA*$ *Institute of Molecular Neurobiology and tDepartment of Ophthalmology, Shiga University of Medical Science, Otsu, 520-21 Japan; and Institutes of tHuman Anatomy and Medical Pharmacology, University "La Sapienza," 00161 Rome, Italy Contributed by Vittorio Erspamer, July 7, 1993 ABSTRACT Using a specific antiserum recently raised comotor activity, sniffing, rearing, grooming (10), as well as against [D-Ala2]deltorphin I (DADTI: Tyr-D-Ala-Phe-Asp-Val- facilitation of social contacts (11) and memory consolidation Val-Gly-NH2), a highly selective ligand for 6-opioid receptors, (12). we have previously demonstrated the occurrence of positive We have recently produced a polyclonal anti-DADTI se- immunostaining in several structures of mouse brain. We rum, which specifically recognizes its carboxyl-terminal tet- describe here the neuroanatomical distribution patterns of rapeptide region (13). Immunohistochemical studies of DADTI-immunoreactive neuronal bodies, axons, and tany- mouse brain have detected DADTI-immunoreactive (IR) cytes in rat brain. Positive neuronal somata were localized neuronal cells in the midbrain tegmentum and positive nerve mainly in the ventral mesencephalon, including the ventral fibers in the accessory olfactory bulb and neostriatum. tegmental area and the pars compacta of the substantia nigra. This study was undertaken to elucidate the neuroanatom- A minor population of positive somata was found in the pars ical distribution patterns of DADTI immunoreactivity in the reticulata and pars lateralis of the substantia nigra, raphe rat brain.
    [Show full text]