DOCSLIB.ORG

A Time-Dependent Role of Midline Thalamic Nuclei in the Retrieval of Fear Memory

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
A Time-Dependent Role of Midline Thalamic Nuclei in the Retrieval of Fear Memory Neuropharmacology 62 (2012) 457e463 Contents lists available at SciVerse ScienceDirect Neuropharmacology journal homepage: www.elsevier.com/locate/neuropharm A time-dependent role of midline thalamic nuclei in the retrieval of fear memory Nancy Padilla-Coreano1, Fabricio H. Do-Monte1, Gregory J. Quirk* Departments of Psychiatry and Anatomy & Neurobiology, University of Puerto Rico School of Medicine, P.O. Box 365067, San Juan 00936, Puerto Rico article info abstract Article history: Increasing evidence indicates that the medial prefrontal cortex (mPFC) and the amygdala mediate Received 6 June 2011 expression and extinction of conditioned fear, but few studies have examined the inputs to these Received in revised form structures. The dorsal part of the midline thalamus (dMT) contains structures such as the mediodorsal 21 August 2011 nucleus, paraventricular nucleus, and paratenial nucleus that project prominently to mPFC, as well as to Accepted 22 August 2011 basal (BA) and central (Ce) nuclei of the amygdala. Using temporary inactivation with GABA agonist muscimol, we found that dMT was necessary for retrieving auditory fear memory that was 24 h old, but Keywords: not 2e8 h old. However, pre-training infusions did not impair fear acquisition or extinction. To determine Thalamus Central amygdala the possible targets of dMT that might modulate fear retrieval, we combined dMT inactivation with Fos Fos immunohistochemistry. Rats with inactivation-induced impairment in fear retrieval showed increased Prefrontal cortex Fos in the lateral division of Ce (CeL), and decreased Fos in the medial division of Ce. No differences in Fos Extinction expression were observed in the mPFC or BA. We suggest that the projections from the paraventricular nucleus to CeL are involved in retrieval of well consolidated fear memories. This article is part of a Special Issue entitled ‘Anxiety and Depression’. Ó 2011 Elsevier Ltd. All rights reserved. 1. Introduction modulate fear retrieval and/or extinction, either via the mPFC or the amygdala. In recent years, there has been renewed interest in the neural Despite anatomical as well as physiological evidence for an circuits mediating the regulation of conditioned fear memories. The influence of dMT on mPFC and amygdala neurons (Ferron et al., medial prefrontal cortex (mPFC) has emerged as a key structure in 1984; Gigg et al., 1994; Pirot et al., 1994; Vives and Mogenson, emotion regulation (Etkin et al., 2011; Quirk and Beer, 2006; Sotres- 1985), relatively few studies have examined dMT’s role in condi- Bayon et al., 2006), and can modulate fear expression bidirection- tioned fear. Regarding fear acquisition, MD lesions reportedly had ally via projections to the amygdala (McDonald, 1991; Quirk and no effect on acquisition or expression of tone conditioning (Garcia Beer, 2006; Sotres-Bayon and Quirk, 2010; Vertes, 2004). Pharma- et al., 2006), but impaired acquisition and expression of context cological inactivation and stimulation studies indicate that the conditioning (Li et al., 2004). Regarding extinction, MD lesions did prelimbic (PL) subregion of the mPFC is essential for fear expression not impair extinction learning or retrieval (Garcia et al., 2006), even (Corcoran and Quirk, 2007; Sierra-Mercado et al., 2011; Vidal- though extinction increases mPFC potentials evoked by MD stim- Gonzalez et al., 2006), whereas the infralimbic subregion (IL) is ulation (Herry and Garcia, 2002; Herry et al., 1999). essential for fear extinction (Kim et al., 2009; Laurent and The lesion approach often underestimates the role of a given Westbrook, 2009; Milad and Quirk, 2002; Sierra-Mercado et al., structure, due to recovery of function by other areas (Anglada- 2011). PL and IL both receive strong input from the dorsal midline Figueroa and Quirk, 2005; Poulos et al., 2010). In light of this, we thalamic nuclei (dMT), including the mediodorsal nucleus recently used the GABAA agonist muscimol to evaluate the contri- (MD) and paraventricular nucleus (PV) (Hoover and Vertes, 2007; butions of prefrontal, hippocampal, and amygdalar areas to the Vertes, 2006). dMT nuclei also project to the basal (BA) and expression and extinction of tone-induced fear (Sierra-Mercado central (Ce) nuclei of the amygdala (Turner and Herkenham, 1991; et al., 2011). In the present study, we used the same technique to Vertes and Hoover, 2008). Thus, dMT nuclei are well situated to evaluate the role of the dMT in fear acquisition, retrieval and extinction. We found that while dMT was not necessary for acquisition or extinction, it was necessary for retrieval of fear memories that were 24 h old, but not 2e8 h old. We extended our * Corresponding author. Tel.: þ787 999 3058; fax: þ787 999 3057. E-mail address: [email protected] (G.J. Quirk). approach with Fos immunohistochemistry (neural activity marker) 1 Contributed equally to this study. to evaluate the effect of dMT inactivation on target areas involved in 0028-3908/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.neuropharm.2011.08.037 458 N. Padilla-Coreano et al. / Neuropharmacology 62 (2012) 457e463 fear regulation. Impaired fear retrieval was correlated with changes 2.6. Immunohistochemistry in Fos expression in Ce, but not in PL, IL or BA. Ninety minutes after fear retrieval, muscimol or saline infused rats were deeply anesthetized with sodium pentobarbital (450 mg/kg i.p.) and perfused transcardially 2. Materials and methods with 100 ml saline (0.9%), followed by 500 ml of 4% paraformaldehyde in 0.1 M phosphate buffer (pH 7.4). Brains were post fixed for 3 h in the same fixative solution 2.1. Subjects and transferred to a solution of 30% sucrose in 0.1 M phosphate buffer at 4 C for 2 nights. Brains were then frozen and a series of 40 mm sections were cut with A total of 108 male Sprague-Dawley rats (Harlan Laboratories, Indianapolis, IN) a cryostat (Leica, CM 1850) in the frontal plane and collected at different levels of the weighing 270e320 g were housed and handled as described previously (Quirk et al., medial prefrontal cortex and amygdala. One complete series of sections was pro- 2000). Rats were restricted to 18 g/day of standard laboratory rat chow, followed by cessed for immunohistochemistry with anti-Fos serum raised in rabbit (Ab-5, training to press a bar for food on a variable interval schedule of reinforcement Oncogene Science) at a dilution of 1:20,000 overnight. The primary antiserum (VI-60). Pressing a bar for food ensures a constant level of activity against which was localized using a variation of the avidinebiotin complex system. Sections were freezing behavior can be reliably measured during long training sessions, and incubated for 120 min at room temperature in a solution of biotinylated goat anti- provides an additional measure of fear (suppression ratio) that is more sensitive rabbit IgG (Vector Laboratories) and then placed in the mixed avidinebiotine than freezing (Quirk et al., 2000). All procedures were approved by the Institutional horseradish peroxidase complex solution (ABC Elite kit, Vector Laboratories) for Animal Care and Use Committee of the University of Puerto Rico, School of Medicine 90 min. Black immunoreactive nuclei labeled for Fos were visualized after 10 min of in compliance with National Institutes of Health guidelines for the care and use of exposure to a chromogen solution containing 0.02% 3,30 diaminobenzidinetetrahy- laboratory animals. drochloride with 0.3% nickel-ammonium sulfate (DAB-Ni) in 0.05 M Tris buffer (pH 7.6) followed by incubation for 5 min in a chromogen solution with glucose oxidase 2.2. Surgery (10%) and D-Glucose (10%). The reaction was stopped using potassium PBS (pH 7,4). Sections were mounted in coated-gelatin slides and then dehydrated and cover After bar-press training, rats were anesthetized with intraperitoneal injections slipped. Counter sections were collected, stained for Nissl bodies, cover slipped and of a mixture of ketamine (80 mg/kg)-xylazine (10 mg/kg) and were stereo- examined in an optical microscope to determine the anatomical boundaries of each taxically implanted with a double 26-gauge guide cannula (Plastics One, Roanoke, structure analyzed. VA, USA) targeting the medial dorsal nucleus of the thalamus (coordinates: ante- À þ À roposterior, 2.5 mm from bregma; mediolateral, / 0.60 mm from midline; 2.7. Immunoreactivity quantification dorsoventral, À4.5 mm from skull surface) (Paxinos and Watson, 1997). Cannulas fi were xed to the skull with dental cement and two stainless steel screws. After Counting of Fos positive cells was carried out at 20Â magnification of an surgery, a triple antibiotic was applied and an analgesic (Ketofen; 2 mg/kg) was Olympus microscope (Model BX51) equipped with a digital camera. Images were injected intramuscularly. Stainless steel obturators (33-gauge) were inserted into generated for PL, IL, basal nucleus of the amygdala (BA), lateral/central nucleus of the the guide cannulas to avoid obstructions until infusions were made. After surgery, central amygdala (CeL/CeC) and medial nucleus of the central amygdala (CeM). To be e animals were allowed to recover 5 7 days before initiating experiments. considered positive for Fos-like immunoreactivity, the nucleus had to be of appro- priate size (area ranging from 100 to 500 mm2) and shape (at least 50% of circularity), 2.3. Histology and be distinct from the background. Fos positive cells were automatically counted and averaged across 2 distinct rostro-caudal sections for each brain structure Upon completion of experiments, rats were transcardially perfused with 0.9% analyzed (Metamorph software version 6.1). The density of Fos positive cells in the saline followed by 10% buffered formalin. Brains were extracted and stored in a 30% CeL/CeC and CeM was calculated by dividing the number of Fos positive cells by the sucrose/10% formalin solution. Coronal sections were cut 40 mm thick, mounted on total area of each region.
Load more

Recommended publications
  • The Human Thalamus Is an Integrative Hub for Functional Brain Networks
    5594 • The Journal of Neuroscience, June 7, 2017 • 37(23):5594–5607 Behavioral/Cognitive The Human Thalamus Is an Integrative Hub for Functional Brain Networks X Kai Hwang, Maxwell A. Bertolero, XWilliam B. Liu, and XMark D’Esposito Helen Wills Neuroscience Institute and Department of Psychology, University of California, Berkeley, Berkeley, California 94720 The thalamus is globally connected with distributed cortical regions, yet the functional significance of this extensive thalamocortical connectivityremainslargelyunknown.Byperforminggraph-theoreticanalysesonthalamocorticalfunctionalconnectivitydatacollected from human participants, we found that most thalamic subdivisions display network properties that are capable of integrating multi- modal information across diverse cortical functional networks. From a meta-analysis of a large dataset of functional brain-imaging experiments, we further found that the thalamus is involved in multiple cognitive functions. Finally, we found that focal thalamic lesions in humans have widespread distal effects, disrupting the modular organization of cortical functional networks. This converging evidence suggests that the human thalamus is a critical hub region that could integrate diverse information being processed throughout the cerebral cortex as well as maintain the modular structure of cortical functional networks. Key words: brain networks; diaschisis; functional connectivity; graph theory; thalamus Significance Statement The thalamus is traditionally viewed as a passive relay station of information from sensory organs or subcortical structures to the cortex. However, the thalamus has extensive connections with the entire cerebral cortex, which can also serve to integrate infor- mation processing between cortical regions. In this study, we demonstrate that multiple thalamic subdivisions display network properties that are capable of integrating information across multiple functional brain networks. Moreover, the thalamus is engaged by tasks requiring multiple cognitive functions.
    [Show full text]
  • Higher-Order Thalamic Relays Burst More Than First-Order Relays
    Higher-order thalamic relays burst more than first-order relays E. J. Ramcharan*, J. W. Gnadt†, and S. M. Sherman‡§ *Center for Complex Systems and Brain Sciences, Florida Atlantic University, 777 Glades Road, Boca Raton, FL 33431; †Department of Neurobiology, State University of New York, Stony Brook, NY 11794-5230; and ‡Department of Neurobiology, Pharmacology, and Physiology, University of Chicago, MC 0926, 316 Abbott, 947 East 58th Street, Chicago, IL 60637 Edited by Robert H. Wurtz, National Institutes of Health, Bethesda, MD, and approved July 11, 2005 (received for review April 6, 2005) There is a strong correlation between the behavior of an animal trasted with the higher-order relays, such as the pulvinar for and the firing mode (burst or tonic) of thalamic relay neurons. vision, the magnocellular (or ‘‘nonlemniscal’’) portion of the Certain differences between first- and higher-order thalamic relays medial geniculate nucleus for hearing, and the posterior medial (which relay peripheral information to the cortex versus informa- nucleus for somesthesis, which are thought to serve as a link in tion from one cortical area to another, respectively) suggest that cortico-thalamo-cortical pathways that continue to process these more bursting might occur in the higher-order relays. Accordingly, information streams. we recorded bursting behavior in single cells from awake, behav- We thought that it would be useful to extend the observations ing rhesus monkeys in first-order (the lateral geniculate nucleus, of bursting to higher-order thalamic relays in the behaving the ventral posterior nucleus, and the ventral portion of the medial monkey for the following reasons.
    [Show full text]
  • MRI Atlas of the Human Deep Brain Jean-Jacques Lemaire
    MRI Atlas of the Human Deep Brain Jean-Jacques Lemaire To cite this version: Jean-Jacques Lemaire. MRI Atlas of the Human Deep Brain. 2019. hal-02116633 HAL Id: hal-02116633 https://hal.uca.fr/hal-02116633 Preprint submitted on 1 May 2019 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Distributed under a Creative Commons Attribution - NonCommercial - NoDerivatives| 4.0 International License MRI ATLAS of the HUMAN DEEP BRAIN Jean-Jacques Lemaire, MD, PhD, neurosurgeon, University Hospital of Clermont-Ferrand, Université Clermont Auvergne, CNRS, SIGMA, France This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/ or send a letter to Creative Commons, PO Box 1866, Mountain View, CA 94042, USA. Terminologia Foundational Model Terminologia MRI Deep Brain Atlas NeuroNames (ID) neuroanatomica usages, classical and french terminologies of Anatomy (ID) Anatomica 1998 (ID) 2017 http://fipat.library.dal.ca In
    [Show full text]
  • Regional Cerebral Glucose Utilization During Morphine Withdrawal in the Rat (Cerebral Metabolism/Limbic System/Drug Dependence) G
    Proc. Natl Acad. Sci. USA Vol. 79, pp. 3360-3364, May 1982 Neurobiology Regional cerebral glucose utilization during morphine withdrawal in the rat (cerebral metabolism/limbic system/drug dependence) G. F. WOOTEN, P. DISTEFANO, AND R. C. COLLINS Departments of Neurology and Pharmacology, Division of Clinical Neuropharmacology, Washington University School of Medicine, St. Louis, Missouri 63110 Communicated by Oliver H. Lowry, February 26, 1982 ABSTRACT Regional cerebral glucose utilization was studied precipitated morphine withdrawal in the rat. A preliminary re- by 2-deoxy['4C]glucose autoradiography in morphine-dependent port of this work has appeared as an abstract (17). rats and during naloxone-induced morphine withdrawal. In mor- phine-dependent rats, glucose utilization was increased compared MATERIALS AND METHODS with naive controls uniformly (23-54%) in hippocampus, dentate gyrus, and subiculum and reduced in frontal cortex, striatum, an- Preparation of Animals. Male Sprague-Dawley rats weigh- terior ventral thalamus, and medial habenular nucleus. On pre- ing 275-325 g were used. On experimental day 1, a single pellet cipitation ofmorphine withdrawal by subcutaneous administration containing 75 mg of morphine as free base was implanted sub- of naloxone at 0.5 mg/kg to morphine-dependent rats, glucose cutaneously under light ether anesthesia. On day 4, two pellets, utilization was increased in the central nucleus ofamygdala (51%), each containing 75 mg of morphine as free base, were im- lateral mammillary nucleus (40%), lateral habenular nucleus planted. On day 7, after being deprived of food for 12 hr, the (39%), medial mammillary nucleus (35%), and medial septal nu- rats were lightly anesthetized with 2% halothane, the pellets cleus (35%) (all, P < 0.01).
    [Show full text]
  • Learning & Memory
    Downloaded from learnmem.cshlp.org on September 27, 2021 - Published by Cold Spring Harbor Laboratory Press Review Unraveling the contributions of the diencephalon to recognition memory: A review John P. Aggleton,1,3 Julie R. Dumont,1 and Elizabeth Clea Warburton2 1School of Psychology, Cardiff University, Cardiff, CF10 3AT, Wales, United Kingdom; 2MRC Centre for Synaptic Plasticity, School of Physiology, University of Bristol, Bristol BS8 1TD, United Kingdom Both clinical investigations and studies with animals reveal nuclei within the diencephalon that are vital for recognition memory (the judgment of prior occurrence). This review seeks to identify these nuclei and to consider why they might be important for recognition memory. Despite the lack of clinical cases with circumscribed pathology within the diencepha- lon and apparent species differences, convergent evidence from a variety of sources implicates a subgroup of medial dien- cephalic nuclei. It is supposed that the key functional interactions of this subgroup of diencephalic nuclei are with the medial temporal lobe, the prefrontal cortex, and with cingulate regions. In addition, some of the clinical evidence most readily supports dual-process models of recognition, which assume two independent cognitive processes (recollective-based and familiarity-based) that combine to direct recognition judgments. From this array of information a “multi-effect multi- nuclei” model is proposed, in which the mammillary bodies and the anterior thalamic nuclei are of preeminent importance for recollective-based recognition. The medial dorsal thalamic nucleus is thought to contribute to familiarity-based recog- nition, but this nucleus, along with various midline and intralaminar thalamic nuclei, is also assumed to have broader, indirect effects upon both recollective-based and familiarity-based recognition.
    [Show full text]
  • Projections of Auditory Cortex to the Medial Geniculate Body of the Cat
    THE JOURNAL OF COMPARATIVE NEUROLOGY 430:27–55 (2001) Projections of Auditory Cortex to the Medial Geniculate Body of the Cat JEFFERY A. WINER,* JAMES J. DIEHL, AND DAVID T. LARUE Division of Neurobiology, Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, California 94720-3200 ABSTRACT The corticofugal projection from 12 auditory cortical fields onto the medial geniculate body was investigated in adult cats by using wheat germ agglutinin conjugated to horserad- ish peroxidase or biotinylated dextran amines. The chief goals were to determine the degree of divergence from single cortical fields, the pattern of convergence from several fields onto a single nucleus, the extent of reciprocal relations between corticothalamic and thalamocortical connections, and to contrast and compare the patterns of auditory corticogeniculate projec- tions with corticofugal input to the inferior colliculus. The main findings were that (1) single areas showed a wide range of divergence, projecting to as few as 5, and to as many as 15, thalamic nuclei; (2) most nuclei received projections from approximately five cortical areas, whereas others were the target of as few as three areas; (3) there was global corticothalamic- thalamocortical reciprocity in every experiment, and there were also significant instances of nonreciprocal projections, with the corticothalamic input often more extensive; (4) the corti- cothalamic projection was far stronger and more divergent than the corticocollicular projec- tion from the same areas, suggesting that the thalamus and the inferior colliculus receive differential degrees of corticofugal control; (5) cochleotopically organized areas had fewer corticothalamic projections than fields in which tonotopy was not a primary feature; and (6) all corticothalamic projections were topographic, focal, and clustered, indicating that areas with limited cochleotopic organization still have some internal spatial arrangement.
    [Show full text]
  • The Hypothalamus and Periaqueductal Gray Are the Sources of Dopamine Fibers in the Paraventricular Nucleus of the Thalamus in Th
    ORIGINAL RESEARCH ARTICLE published: 20 November 2014 NEUROANATOMY doi: 10.3389/fnana.2014.00136 The hypothalamus and periaqueductal gray are the sources of dopamine fibers in the paraventricular nucleus of the thalamus in the rat Sa Li 1,2, Yuxiu Shi 1* and Gilbert J. Kirouac 2,3 1 PTSD Laboratory, Department of Histology and Embryology, Institute of Pathology and Pathophysiology, China Medical University, Shenyang, China 2 Department of Oral Biology, Faculty of Dentistry, University of Manitoba, Winnipeg, MB, Canada 3 Department of Psychiatry, Faculty of Medicine, University of Manitoba, Winnipeg, MB, Canada Edited by: The paraventricular nucleus of the thalamus (PVT) sends a very dense projection to the Kathleen S. Rockland, Boston nucleus accumbens. This area of the striatum plays a key role in motivation and recent University School Medicine, USA experimental evidence indicates that the PVT may have a similar function. It is well known Reviewed by: Ariel Y. Deutch, Vanderbilt that a dopaminergic projection from the ventral tegmental area (VTA) to the nucleus University Medical Center, USA accumbens is a key regulator of motivation and reward-related behavior. Dopamine (DA) Carmen Cavada, Universidad fibers have also been localized in the PVT but the source of these fibers in the rat Autonoma de Madrid, Spain has not been unequivocally identified. The present study was done to re-examine this *Correspondence: question. Small iontophoretic injections of cholera toxin B (CTb) were made in the PVT Yuxiu Shi, PTSD Laboratory, Department of Histology and to retrogradely label tyrosine hydroxylase (TH) neurons. Neurons that were double-labeled Embryology, Institute of Pathology for TH/CTb were found scattered in DA cell groups of the hypothalamus (ventrorostral and Pathophysiology, China Medical A10, A11, A13, A15 DA cell groups) and the midbrain (dorsocaudal A10 embedded in the University, Basic Medical Sciences periaqueductal gray).
    [Show full text]
  • Amygdalar Interaction with the Mediodorsal Nucleus of the Thalamus and the Ventromedial Prefrontal Cortex in Stimulus-Reward Associative Learning in the Monkey
    The Journal of Neuroscience, November 1990, fO(11): 3479-3493 Amygdalar Interaction with the Mediodorsal Nucleus of the Thalamus and the Ventromedial Prefrontal Cortex in Stimulus-Reward Associative Learning in the Monkey David Gaffan’ and Elisabeth A. Murray* ‘Department of Experimental Psychology, Oxford University, Oxford OX1 3UD, England, and *Laboratory of Neuropsychology, National Institute of Mental Health, Bethesda, Maryland 20892 Cynomolgus monkeys (Macaca fascicularis) were assessed One kind of associative learning in which the amygdala is of for their ability to associate visual stimuli with food reward. central importance is the associationof a sensorystimulus with They learned a series of new 2-choice visual discriminations the incentive value of food reward. In visual-discrimination between colored patterns displayed on a monitor screen. learning for food reward, the role of the amygdala varies ac- The feedback for correct choice was the delivery of food. In cording to the associative structure of the task. If visual dis- order to promote associative learning between the visual criminative stimuli are associateddirectly with the incentive stimuli and the incentive value of the food reward, reward value of the food reward, efficient learning dependson an in- delivery was not accompanied by any distinctive visual feed- trahemispheric interaction between the amygdala and the vi- back on the display screen. The rate of learning new prob- sual-associationcortex ipsilateral to it (E. A. Gaffan et al., 1988). lems was assessed before and after surgery in a total of 16 But when visual discriminative stimuli are associatedwith the monkeys. Three groups of 3 monkeys received bilaterally incentive value indirectly, via the mediation of a direct asso- symmetrical ablations in either the amygdala, the medio- ciation with an auditory or visual secondary reinforcer, visual dorsal nucleus of the thalamus, or the ventromedial pre- interaction with the amygdala is less important (Gaffan and frontal cortex.
    [Show full text]
  • Hypothesis-Driven Structural Connectivity Analysis Supports Network Over Hierarchical Model of Brain Architecture
    Hypothesis-driven structural connectivity analysis supports network over hierarchical model of brain architecture Richard H. Thompson and Larry W. Swanson1 Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089 Contributed by Larry W. Swanson, June 30, 2010 (sent for review May 14, 2010) The brain is usually described as hierarchically organized, although (9) and a massive input from the SUBv (10). Only two major an alternative network model has been proposed. To help distin- brainstem inputs were identified: the dorsal raphé (DR), the guish between these two fundamentally different structure-function presumptive source of ACBdmt serotonin (11), and the inter- hypotheses, we developed an experimental circuit-tracing strategy fascicular nucleus (IF), the presumptive source of ACBdmt do- that can be applied to any starting point in the nervous system and pamine (12) that is medial to the expected ventral tegmental area then systematically expanded, and applied it to a previously obscure (VTA) itself (13). Thus, the ACBdmt receives direct inputs from dorsomedial corner of the nucleus accumbens identified functionally three massively interconnected cerebral regions implicated in as a “hedonic hot spot.” A highly topographically organized set of stress and depression, as well as restricted brainstem sites pro- connections involving expected and unexpected gray matter regions viding dopaminergic and serotonergic terminals. was identified that prominently features regions associated with Only one ACBdmt axonal output was labeled with PHAL (Fig. appetite, stress, and clinical depression. These connections are 1A; the filled purple area is a representative injection site): a arranged as a longitudinal series of circuits (closed loops). Thus, the descending pathway through the medial forebrain bundle with two results do not support a rigidly hierarchical model of nervous system clear terminal fields.
    [Show full text]
  • Fmri Assessment of the Pulvinar and Medial Dorsal Nucleus in Normal Volunteers Monte S
    Neuroscience Letters 404 (2006) 282–287 Thalamocortical circuits: fMRI assessment of the pulvinar and medial dorsal nucleus in normal volunteers Monte S. Buchsbaum a,∗, Bradley R. Buchsbaum b, Sylvie Chokron c,d, Cheuk Tang a,e, Tse-Chung Wei a, William Byne a,f a Department of Psychiatry, Mount Sinai School of Medicine, Box 1505, New York, NY 10029-6574, USA b Unit on Integrative Neuroimaging, Clinical Brain Disorders Branch, NIMH, NIH, Bethesda, MD, USA c Laboratoire de Psychologie Experimentale, CNRS, UMR 5105, Grenoble, France d Service de Neurologie, Fondation Ophtalmologique Rothschild, Paris, France e Department of Radiology, Mount Sinai School of Medicine, New York, NY, USA f Bronx VA Medical Center, Bronx, NY, USA Received 27 September 2005; received in revised form 10 March 2006; accepted 15 May 2006 Abstract This fMRI study investigates the activation of the thalamic nuclei in a spatial focusing-of-attention task previously shown to activate the pulvinar with FDG-PET and assesses the connectivity of the thalamic nuclei with cortical areas. Normal right-handed subjects (eight men, eight women, average age = 32 years) viewed four types of stimuli positioned to the right or left of the central fixation point (left hemifield-large letter, left hemifield-small letter display with flanking letters; right hemifield-large letter, right hemifield-small letter display with flankers). BOLD responses to small letters surrounded by flankers were compared with responses to large isolated letters. To examine maximum functional regional connectivity, we modeled “subject” as a random effect and attained fixed effect parameter estimates and t-statistics for functional connectivity between each of the thalamic nuclei (pulvinar, medial dorsal, and anterior) as the seed region and each non-seed voxel.
    [Show full text]
  • Medial Geniculate Lesions Block Amygdalar and Cingulothalamic Learning-Related Neuronal Activity
    The Journal of Neuroscience, November 1, 1997, 17(21):8645–8655 Medial Geniculate Lesions Block Amygdalar and Cingulothalamic Learning-Related Neuronal Activity Amy Poremba1 and Michael Gabriel2 1Department of Psychology and Institute for Neuroscience, Univsity of Texas, Austin, Texas 78712, and 2Department of Psychology and Beckman Institute, University of Illinois, Urbana, Illinois 61801 This study assessed the role of the thalamic medial geniculate anterior-ventral and medial-dorsal thalamic nuclei, and the ba- (MG) nucleus in discriminative avoidance learning, wherein rab- solateral nucleus of the amygdala before training. Learning was bits acquire a locomotory response to a tone [conditioned severely impaired and TIA was abolished in all areas in rabbits stimulus (CS)1] to avoid a foot shock, and they learn to ignore with lesions. Thus learning and TIA require the integrity of the a different tone (CS2) not predictive of foot shock. Limbic MG nucleus. Only damage in the medial MG division was (anterior and medial dorsal) thalamic, cingulate cortical, or significantly correlated with the learning deficit. The lesions amygdalar lesions severely impair acquisition, and neurons in abolished the sensory response of amygdalar neurons, and these areas develop training-induced activity (TIA): more firing they attenuated (but did not eliminate) the sensory response of to the CS1 than to the CS2. MG neurons exhibit TIA during cingulothalamic neurons, suggesting the existence of extra learning and project to the amygdala. The MG neurons may geniculate
    [Show full text]
  • Download English-US Transcript (PDF)
    MITOCW | MIT9_14S14_lec29.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 ocw.mit.edu. PROFESSOR: OK, instead of a quiz I'm trying to write some homework. And some of them will be extra credit, some of them will be part of the required homework. Now today we still have a lot to do on chapter 26 concerning core pathways of the limbic system. And this is where we finished last time. We may not even get to the part on hormones and brain development and effects on the brain, but we may just do most of that with the reading because I really need the time to talk to you about the recent changes in understanding of the hippocampus and the pathways related to it. OK, we answered this question with the information about the internal environment in the body reaches the hypothalamus via both the bloodstream and sensory pathways. And then I asked this about, well, how do these molecules even get in the brain? We know that there's a blood-brain barrier. Very small molecules can get in, but not the larger, organic molecules. And yet, things like angiotensin II do get in, but they get in only at certain places. Places where the blood-brain barrier is weak. I think the figure in the book is a little better than this one, but this is a similar one.
    [Show full text]