Update on Models of Basal Ganglia Function and Dysfunction
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The Department of Neurobiology & Anatomy and the Motor
The Neuroscience Graduate Program presents: SHIONA BISWAS ADVISOR: LIN GAN IN A PHD THESIS DEFENSE WEDNESDAY, 28 SEPTEMBER 2016 10:00AM IN WHIPPLE AUDITORIUM (2-6424) The transcription regulator Lmo3 is required for correct cell fate specification in the external globus pallidus. The external globus pallidus (GPe), a core component of the basal ganglia, can powerfully influence the processing of motor information due to its widespread projections to almost all basal ganglia nuclei. Aberrant activity of GPe neurons has been linked to motor symptoms of a variety of movement disorders, such as Parkinson’s Disease, Huntington’s disease and dystonia. While several decades of work had suggested the existence of heterogeneity within GPe GABAergic projection neurons, it is not until recent years that multiple molecular markers have been established to unambiguously define and distinguish between two main GPe neuronal subtypes: the prototypic and arkypallidal neurons. This demarcation is also based on their unique projection patterns, membrane properties and ion channel expression, and consequently, distinct electrophysiological profiles, in both healthy and diseased (Parkinsonian) states. As a result of this, we now have an improved understanding of how these neurons function and encode motor behavior in both healthy and diseased states. A few studies have established some of the basic aspects of GPe development- such as the parts of the developing forebrain from which GPe neurons originate and the embryonic time points during which they are born. However, specific molecular factors required for the development of GPe neurons remain unexplored. For my thesis project, I studied the role of the transcription regulator, Lmo3, in the specification of subsets of external globus pallidus neurons. -
Basal Ganglia & Cerebellum
1/2/2019 This power point is made available as an educational resource or study aid for your use only. This presentation may not be duplicated for others and should not be redistributed or posted anywhere on the internet or on any personal websites. Your use of this resource is with the acknowledgment and acceptance of those restrictions. Basal Ganglia & Cerebellum – a quick overview MHD-Neuroanatomy – Neuroscience Block Gregory Gruener, MD, MBA, MHPE Vice Dean for Education, SSOM Professor, Department of Neurology LUHS a member of Trinity Health Outcomes you want to accomplish Basal ganglia review Define and identify the major divisions of the basal ganglia List the major basal ganglia functional loops and roles List the components of the basal ganglia functional “circuitry” and associated neurotransmitters Describe the direct and indirect motor pathways and relevance/role of the substantia nigra compacta 1 1/2/2019 Basal Ganglia Terminology Striatum Caudate nucleus Nucleus accumbens Putamen Globus pallidus (pallidum) internal segment (GPi) external segment (GPe) Subthalamic nucleus Substantia nigra compact part (SNc) reticular part (SNr) Basal ganglia “circuitry” • BG have no major outputs to LMNs – Influence LMNs via the cerebral cortex • Input to striatum from cortex is excitatory – Glutamate is the neurotransmitter • Principal output from BG is via GPi + SNr – Output to thalamus, GABA is the neurotransmitter • Thalamocortical projections are excitatory – Concerned with motor “intention” • Balance of excitatory & inhibitory inputs to striatum, determine whether thalamus is suppressed BG circuits are parallel loops • Motor loop – Concerned with learned movements • Cognitive loop – Concerned with motor “intention” • Limbic loop – Emotional aspects of movements • Oculomotor loop – Concerned with voluntary saccades (fast eye-movements) 2 1/2/2019 Basal ganglia “circuitry” Cortex Striatum Thalamus GPi + SNr Nolte. -
Basal Ganglia Anatomy, Physiology, and Function Ns201c
Basal Ganglia Anatomy, Physiology, and Function NS201c Human Basal Ganglia Anatomy Basal Ganglia Circuits: The ‘Classical’ Model of Direct and Indirect Pathway Function Motor Cortex Premotor Cortex + Glutamate Striatum GPe GPi/SNr Dopamine + - GABA - Motor Thalamus SNc STN Analagous rodent basal ganglia nuclei Gross anatomy of the striatum: gateway to the basal ganglia rodent Dorsomedial striatum: -Inputs predominantly from mPFC, thalamus, VTA Dorsolateral striatum: -Inputs from sensorimotor cortex, thalamus, SNc Ventral striatum: Striatal subregions: Dorsomedial (caudate) -Inputs from vPFC, hippocampus, amygdala, Dorsolateral (putamen) thalamus, VTA Ventral (nucleus accumbens) Gross anatomy of the striatum: patch and matrix compartments Patch/Striosome: -substance P -mu-opioid receptor Matrix: -ChAT and AChE -somatostatin Microanatomy of the striatum: cell types Projection neurons: MSN: medium spiny neuron (GABA) •striatonigral projecting – ‘direct pathway’ •striatopallidal projecting – ‘indirect pathway’ Interneurons: FS: fast-spiking interneuron (GABA) LTS: low-threshold spiking interneuron (GABA) LA: large aspiny neuron (ACh) 30 um Cellular properties of striatal neurons Microanatomy of the striatum: striatal microcircuits • Feedforward inhibition (mediated by fast-spiking interneurons) • Lateral feedback inhibition (mediated by MSN collaterals) Basal Ganglia Circuits: The ‘Classical’ Model of Direct and Indirect Pathway Function Motor Cortex Premotor Cortex + Glutamate Striatum GPe GPi/SNr Dopamine + - GABA - Motor Thalamus SNc STN The simplified ‘classical’ model of basal ganglia circuit function • Information encoded as firing rate • Basal ganglia circuit is linear and unidirectional • Dopamine exerts opposing effects on direct and indirect pathway MSNs Basal ganglia motor circuit: direct pathway Motor Cortex Premotor Cortex Glutamate Striatum GPe GPi/SNr Dopamine + GABA Motor Thalamus SNc STN Direct pathway MSNs express: D1, M4 receptors, Sub. -
Neural Plasticity in the Brain During Neuropathic Pain
biomedicines Review Neural Plasticity in the Brain during Neuropathic Pain Myeong Seong Bak 1, Haney Park 1 and Sun Kwang Kim 1,2,* 1 Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Seoul 02447, Korea; [email protected] (M.S.B.); [email protected] (H.P.) 2 Department of Physiology, College of Korean Medicine, Kyung Hee University, Seoul 02447, Korea * Correspondence: [email protected]; Tel.: +82-2-961-0491 Abstract: Neuropathic pain is an intractable chronic pain, caused by damage to the somatosensory nervous system. To date, treatment for neuropathic pain has limited effects. For the development of efficient therapeutic methods, it is essential to fully understand the pathological mechanisms of neuropathic pain. Besides abnormal sensitization in the periphery and spinal cord, accumulating evidence suggests that neural plasticity in the brain is also critical for the development and mainte- nance of this pain. Recent technological advances in the measurement and manipulation of neuronal activity allow us to understand maladaptive plastic changes in the brain during neuropathic pain more precisely and modulate brain activity to reverse pain states at the preclinical and clinical levels. In this review paper, we discuss the current understanding of pathological neural plasticity in the four pain-related brain areas: the primary somatosensory cortex, the anterior cingulate cortex, the periaqueductal gray, and the basal ganglia. We also discuss potential treatments for neuropathic pain based on the modulation of neural plasticity in these brain areas. Keywords: neuropathic pain; neural plasticity; primary somatosensory cortex; anterior cingulate cortex; periaqueductal grey; basal ganglia Citation: Bak, M.S.; Park, H.; Kim, S.K. -
Neural Circuit and Clinical Insights from Intraoperative Recordings During Deep Brain Stimulation Surgery
brain sciences Perspective Neural Circuit and Clinical Insights from Intraoperative Recordings During Deep Brain Stimulation Surgery Anand Tekriwal 1,2,3 , Neema Moin Afshar 2, Juan Santiago-Moreno 3, Fiene Marie Kuijper 4, Drew S. Kern 1,5, Casey H. Halpern 4, Gidon Felsen 2 and John A. Thompson 1,5,* 1 Department of Neurosurgery, University of Colorado School of Medicine, Aurora, CO 80203, USA 2 Department of Physiology and Biophysics, University of Colorado School of Medicine, Aurora, CO 80203, USA 3 Medical Scientist Training Program, University of Colorado School of Medicine, Aurora, CO 80203, USA 4 Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA 94305, USA 5 Department of Neurology, University of Colorado School of Medicine, Aurora, CO 80203, USA * Correspondence: [email protected] Received: 28 June 2019; Accepted: 18 July 2019; Published: 20 July 2019 Abstract: Observations using invasive neural recordings from patient populations undergoing neurosurgical interventions have led to critical breakthroughs in our understanding of human neural circuit function and malfunction. The opportunity to interact with patients during neurophysiological mapping allowed for early insights in functional localization to improve surgical outcomes, but has since expanded into exploring fundamental aspects of human cognition including reward processing, language, the storage and retrieval of memory, decision-making, as well as sensory and motor processing. The increasing use of chronic neuromodulation, via deep brain stimulation, for a spectrum of neurological and psychiatric conditions has in tandem led to increased opportunity for linking theories of cognitive processing and neural circuit function. Our purpose here is to motivate the neuroscience and neurosurgical community to capitalize on the opportunities that this next decade will bring. -
Different Roles of Direct and Indirect Frontoparietal Pathways for Individual Working Memory Capacity
2894 • The Journal of Neuroscience, March 9, 2016 • 36(10):2894–2903 Behavioral/Cognitive Different Roles of Direct and Indirect Frontoparietal Pathways for Individual Working Memory Capacity X Matthias Ekman,1,2 Christian J. Fiebach,1,3,4 Corina Melzer,2 XMarc Tittgemeyer,2 and Jan Derrfuss1,2 1Radboud University Nijmegen, Donders Institute for Brain, Cognition and Behaviour, 6500 HE Nijmegen, The Netherlands, 2Max Planck Institute for Neurological Research, 50931 Cologne, Germany, 3Department of Psychology, Goethe University Frankfurt, 60323 Frankfurt am Main, Germany, and 4Center for Individual Development and Adaptive Education, 60486 Frankfurt am Main, Germany The ability to temporarily store and manipulate information in working memory is a hallmark of human intelligence and differs consid- erably across individuals, but the structural brain correlates underlying these differences in working memory capacity (WMC) are only poorly understood. In two separate studies, diffusion MRI data and WMC scores were collected for 70 and 109 healthy individuals. Using a combination of probabilistic tractography and network analysis of the white matter tracts, we examined whether structural brain network properties were predictive of individual WMC. Converging evidence from both studies showed that lateral prefrontal cortex and posterior parietal cortex of high-capacity individuals are more densely connected compared with low-capacity individuals. Importantly, our network approach was further able to dissociate putative functional roles associated with two different pathways connecting frontal and parietal regions: a corticocortical pathway and a subcortical pathway. In Study 1, where participants were required to maintain and update working memory items, the connectivity of the direct and indirect pathway was predictive of WMC. -
A Hierarchical Interpretation of the Functional Organization of the Basal Ganglia
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by PubMed Central HYPOTHESIS AND THEORY ARTICLE published: 11 March 2011 SYSTEMS NEUROSCIENCE doi: 10.3389/fnsys.2011.00013 The arbitration–extension hypothesis: a hierarchical interpretation of the functional organization of the basal ganglia Iman Kamali Sarvestani1,2*, Mikael Lindahl1,2, Jeanette Hellgren-Kotaleski1,2,3 and Örjan Ekeberg1,2 1 Department of Computational Biology, School of Computer Science and Communication, Royal Institute of Technology, Stockholm, Sweden 2 Stockholm Brain Institute, Stockholm, Sweden 3 Department of Neuroscience, Karolinska Institute, Stockholm, Sweden Edited by: Based on known anatomy and physiology, we present a hypothesis where the basal ganglia Federico Bermudez-Rattoni, motor loop is hierarchically organized in two main subsystems: the arbitration system and Universidad Nacional Autónoma de México, Mexico the extension system. The arbitration system, comprised of the subthalamic nucleus, globus Reviewed by: pallidus, and pedunculopontine nucleus, serves the role of selecting one out of several candidate Federico Bermudez-Rattoni, actions as they are ascending from various brain stem motor regions and aggregated in the Universidad Nacional Autónoma de centromedian thalamus or descending from the extension system or from the cerebral cortex. México, Mexico This system is an action-input/action-output system whose winner-take-all mechanism finds Jose Bargas, Universidad Nacional Autónoma de México, Mexico the strongest response among several candidates to execute. This decision is communicated *Correspondence: back to the brain stem by facilitating the desired action via cholinergic/glutamatergic projections Iman Kamali Sarvestani, Department and suppressing conflicting alternatives via GABAergic connections. -
Motor Systems Basal Ganglia
Motor systems 409 Basal Ganglia You have just read about the different motor-related cortical areas. Premotor areas are involved in planning, while MI is involved in execution. What you don’t know is that the cortical areas involved in movement control need “help” from other brain circuits in order to smoothly orchestrate motor behaviors. One of these circuits involves a group of structures deep in the brain called the basal ganglia. While their exact motor function is still debated, the basal ganglia clearly regulate movement. Without information from the basal ganglia, the cortex is unable to properly direct motor control, and the deficits seen in Parkinson’s and Huntington’s disease and related movement disorders become apparent. Let’s start with the anatomy of the basal ganglia. The important “players” are identified in the adjacent figure. The caudate and putamen have similar functions, and we will consider them as one in this discussion. Together the caudate and putamen are called the neostriatum or simply striatum. All input to the basal ganglia circuit comes via the striatum. This input comes mainly from motor cortical areas. Notice that the caudate (L. tail) appears twice in many frontal brain sections. This is because the caudate curves around with the lateral ventricle. The head of the caudate is most anterior. It gives rise to a body whose “tail” extends with the ventricle into the temporal lobe (the “ball” at the end of the tail is the amygdala, whose limbic functions you will learn about later). Medial to the putamen is the globus pallidus (GP). -
Npas1+-Nkx2.1+ Neurons Are an Integral Part of the Cortico-Pallido-Cortical Loop
Research Articles: Cellular/Molecular Npas1+-Nkx2.1+ Neurons Are an Integral Part of the Cortico-pallido-cortical Loop https://doi.org/10.1523/JNEUROSCI.1199-19.2019 Cite as: J. Neurosci 2019; 10.1523/JNEUROSCI.1199-19.2019 Received: 22 May 2019 Revised: 21 November 2019 Accepted: 26 November 2019 This Early Release article has been peer-reviewed and accepted, but has not been through the composition and copyediting processes. The final version may differ slightly in style or formatting and will contain links to any extended data. Alerts: Sign up at www.jneurosci.org/alerts to receive customized email alerts when the fully formatted version of this article is published. Copyright © 2019 the authors 1 + + 2 Npas1 -Nkx2.1 Neurons Are an Integral Part of the Cortico-pallido-cortical 3 Loop 4 5 Zachary A. Abecassis1*, Brianna L. Berceau1*, Phyo H. Win1, Daniela Garcia1, Harry S. Xenias1, Qiaoling Cui1, 6 Arin Pamukcu1, Suraj Cherian1, Vivian M. Hernández1, Uree Chon2, Byung Kook Lim3, Yongsoo Kim2 , 7 Nicholas J. Justice4,5, Raj Awatramani6, Bryan M. Hooks7, Charles R. Gerfen8, Simina M. Boca9, C. Savio 8 Chan1 9 10 1 Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA 11 2 Department of Neural and Behavioral Sciences, College of Medicine, Penn State University, Hershey, PA, 12 USA 13 3 Neurobiology Section, Biological Sciences Division, University of California San Diego, La Jolla, CA, USA 14 4 Center for Metabolic and degenerative disease, Institute of Molecular Medicine, University of Texas, -
Understanding the Role of Cholinergic Tone in the Pedunculopontine Tegmental Nucleus
Western University Scholarship@Western Electronic Thesis and Dissertation Repository 7-22-2014 12:00 AM Understanding the role of cholinergic tone in the pedunculopontine tegmental nucleus Kaie Rosborough The University of Western Ontario Supervisor Dr. Vania Prado The University of Western Ontario Graduate Program in Anatomy and Cell Biology A thesis submitted in partial fulfillment of the equirr ements for the degree in Master of Science © Kaie Rosborough 2014 Follow this and additional works at: https://ir.lib.uwo.ca/etd Part of the Behavioral Neurobiology Commons Recommended Citation Rosborough, Kaie, "Understanding the role of cholinergic tone in the pedunculopontine tegmental nucleus" (2014). Electronic Thesis and Dissertation Repository. 2388. https://ir.lib.uwo.ca/etd/2388 This Dissertation/Thesis is brought to you for free and open access by Scholarship@Western. It has been accepted for inclusion in Electronic Thesis and Dissertation Repository by an authorized administrator of Scholarship@Western. For more information, please contact [email protected]. UNDERSTANDING THE ROLE OF CHOLINERGIC TONE IN THE PEDUNCULOPONTINE TEGMENTAL NUCLEUS Thesis format: Monograph Article by Kaie Rosborough Graduate Program in Anatomy and Cell Biology A thesis submitted in partial fulfillment of the requirements for the degree of Masters of Science The School of Graduate and Postdoctoral Studies The University of Western Ontario London, Ontario, Canada © Kaie Rosborough 2014 ! Abstract To better understand the role of cholinergic signaling in specific regions of the brain, several genetically modified mice targeting the vesicular acetylcholine transporter (VAChT) gene have been generated (Prado et al., 2006; Guzman et al., 2011; de Castro et al., 2009). VAChT stores acetylcholine (ACh) in synaptic vesicles, and changes in this transporter expression directly interferes with ACh release. -
Differential Synaptic Input to External Globus Pallidus Neuronal Subpopulations in Vivo
bioRxiv preprint doi: https://doi.org/10.1101/2020.02.27.967869; this version posted February 28, 2020. 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-NC-ND 4.0 International license. Differential Synaptic Input to External Globus Pallidus Neuronal Subpopulations In Vivo. Maya Ketzef & Gilad Silberberg Department of Neuroscience, Karolinska Institutet, Stockholm 17177, Sweden. Lead contact: Gilad Silberberg Corresponding authors: [email protected] & [email protected] Summary The rodent external Globus Pallidus (GPe) contains two main neuronal subpopulations, prototypic and arkypallidal cells, which differ in their cellular properties. Their functional synaptic connectivity is, however, largely unknown. Here, we studied the membrane properties and synaptic inputs to these subpopulations in the mouse GPe. We obtained in vivo whole-cell recordings from identified GPe neurons and used optogenetic stimulation to dissect their afferent inputs from the striatum and subthalamic nucleus (STN). All GPe neurons received barrages of excitatory and inhibitory input during slow wave activity. The modulation of their activity was cell-type specific and shaped by their respective membrane properties and afferent inputs. Both GPe subpopulations received synaptic input from STN and striatal projection neurons (MSNs). STN and indirect pathway MSNs strongly targeted prototypic cells while direct pathway MSNs selectively inhibited arkypallidal cells. We show that GPe subtypes are differently embedded in the basal ganglia network, supporting distinct functional roles. Keywords: external globus pallidus, in vivo, whole-cell recordings, optogenetics, arkypallidal, prototypic, striatum, subthalamic nucleus, excitation inhibition balance, 1 bioRxiv preprint doi: https://doi.org/10.1101/2020.02.27.967869; this version posted February 28, 2020. -
New Roles for the External Globus Pallidus in Basal Ganglia Circuits and Behavior
15178 • The Journal of Neuroscience, November 12, 2014 • 34(46):15178–15183 Symposium New Roles for the External Globus Pallidus in Basal Ganglia Circuits and Behavior X Aryn H. Gittis,1,2 XJoshua D. Berke,3 Mark D. Bevan,4 C. Savio Chan,4 Nicolas Mallet,5 XMichelle M. Morrow,6,7 and Robert Schmidt8 1Department of Biological Sciences and 2Center for the Neural Basis of Cognition, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213, 3Department of Psychology, Department of Biomedical Engineering, and Neuroscience Program, University of Michigan, Ann Arbor, Michigan 48109, 4Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 48109, 5Institut des maladies neurode´ge´ne´ratives, CNRS UMR 5293, Universite´ de Bordeaux, 33076 Bordeaux, France, 6Center for the Neural Basis of Cognition and 7Systems Neuroscience Institute, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, and 8BrainLinks-BrainTools, Bernstein Center Freiburg, University of Freiburg, Freiburg 79085, Germany The development of methodology to identify specific cell populations and circuits within the basal ganglia is rapidly transforming our ability to understand the function of this complex circuit. This mini-symposium highlights recent advances in delineating the organiza- tion and function of neural circuits in the external segment of the globus pallidus (GPe). Although long considered a homogeneous structure in the motor-suppressing “indirect-pathway,” the GPe consists of a number of distinct cell types and anatomical subdomains that contribute differentially to both motor and nonmotor features of behavior. Here, we integrate recent studies using techniques, such as viral tracing, transgenic mice, electrophysiology, and behavioral approaches, to create a revised framework for understanding how the GPe relates to behavior in both health and disease.