Introduction to Neuroscience: the Basal Ganglia
Total Page:16
File Type:pdf, Size:1020Kb
Load more
Recommended publications
-
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. -
Substance P and Antagonists of the Neurokinin-1 Receptor In
Martinez AN and Philipp MT, J Neurol Neuromed (2016) 1(2): 29-36 Neuromedicine www.jneurology.com www.jneurology.com Journal of Neurology & Neuromedicine Mini Review Article Open Access Substance P and Antagonists of the Neurokinin-1 Receptor in Neuroinflammation Associated with Infectious and Neurodegenerative Diseases of the Central Nervous System Alejandra N. Martinez1 and Mario T. Philipp1,2* 1Division of Bacteriology & Parasitology, Tulane National Primate Research Center, Covington, LA, USA 2Department of Microbiology and Immunology, Tulane University Medical School, New Orleans, LA, USA Article Info ABSTRACT Article Notes This review addresses the role that substance P (SP) and its preferred receptor Received: May 03, 2016 neurokinin-1 (NK1R) play in neuroinflammation associated with select bacterial, Accepted: May 18, 2016 viral, parasitic, and neurodegenerative diseases of the central nervous system. *Correspondence: The SP/NK1R complex is a key player in the interaction between the immune Division of Bacteriology and Parasitology and nervous systems. A common effect of this interaction is inflammation. For Tulane National Primate Research Center this reason and because of the predominance in the human brain of the NK1R, Covington, LA, USA its antagonists are attractive potential therapeutic agents. Preventing the Email: [email protected] deleterious effects of SP through the use of NK1R antagonists has been shown © 2016 Philipp MT. This article is distributed under the terms of to be a promising therapeutic strategy, as these antagonists are selective, the Creative Commons Attribution 4.0 International License potent, and safe. Here we evaluate their utility in the treatment of different neuroinfectious and neuroinflammatory diseases, as a novel approach to Keywords clinical management of CNS inflammation. -
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. -
Conditional Ablation of Brain-Derived Neurotrophic Factor-Trkb Signaling Impairs Striatal Neuron Development
Conditional ablation of brain-derived neurotrophic factor-TrkB signaling impairs striatal neuron development Yun Lia,1, Daishi Yuia, Bryan W. Luikarta,2, Renée M. McKaya, Yanjiao Lia, John L. Rubensteinb, and Luis F. Paradaa,3 aDepartment of Developmental Biology and Kent Waldrep Center for Basic Research on Nerve Growth and Regeneration, University of Texas Southwestern Medical Center, Dallas, TX 75390; and bNina Ireland Laboratory of Developmental Neurobiology, Department of Psychiatry, University of California, San Francisco, CA 94143 Contributed by Luis F. Parada, August 2, 2012 (sent for review June 21, 2012) Neurotrophic factors, such as brain-derived neurotrophic factor cascades pertaining to development, maturation, and function of (BDNF), are associated with the physiology of the striatum and the striatum remains to be delineated. the loss of its normal functioning under pathological conditions. In this study, we conditionally ablated BDNF or its receptor The role of BDNF and its downstream signaling in regulating the TrkB in corticostriatal and nigrostriatal neuronal circuits. We development of the striatum has not been fully investigated, found that Bdnf deletion in both cortex and substantia nigra led to Bdnf complete depletion of BDNF protein in the striatum. Mutant mice however. Here we report that ablation of in both the cortex displayed dramatic developmental abnormalities and neurological and substantia nigra depletes BDNF in the striatum, and leads to impairments. Furthermore, specific deletion of TrkB from striatal fi impaired striatal development, severe motor de cits, and postnatal neurons was sufficient to produce this wide range of developmental lethality. Furthermore, striatal-specific ablation of TrkB, the gene deficits. Thus, our results demonstrate that BDNF and TrkB play encoding the high-affinity receptor for BDNF, is sufficient to elicit critical paracrine and cell-autonomous roles, respectively, in the an array of striatal developmental abnormalities, including de- development and maintenance of striatal neurons. -
Characterization of Substantia Nigra
Mourtzi et al. Stem Cell Research & Therapy (2021) 12:335 https://doi.org/10.1186/s13287-021-02398-3 RESEARCH Open Access Characterization of substantia nigra neurogenesis in homeostasis and dopaminergic degeneration: beneficial effects of the microneurotrophin BNN-20 Theodora Mourtzi1,2*, Dimitrios Dimitrakopoulos2†, Dimitrios Kakogiannis2†, Charalampos Salodimitris2, Konstantinos Botsakis1, Danai Kassandra Meri2, Maria Anesti2,3, Aggeliki Dimopoulou1, Ioannis Charalampopoulos4,5, Achilleas Gravanis4,5, Nikolaos Matsokis3, Fevronia Angelatou1† and Ilias Kazanis2*† Abstract Background: Loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) underlines much of the pathology of Parkinson’s disease (PD), but the existence of an endogenous neurogenic system that could be targeted as a therapeutic strategy has been controversial. BNN-20 is a synthetic, BDNF-mimicking, microneurotrophin that we previously showed to exhibit a pleiotropic neuroprotective effect on the dopaminergic neurons of the SNpc in the “weaver” mouse model of PD. Here, we assessed its potential effects on neurogenesis. Methods: We quantified total numbers of dopaminergic neurons in the SNpc of wild-type and “weaver” mice, with or without administration of BNN-20, and we employed BrdU labelling and intracerebroventricular injections of DiI to evaluate the existence of dopaminergic neurogenesis in the SNpc and to assess the origin of newborn dopaminergic neurons. The in vivo experiments were complemented by in vitro proliferation/differentiation assays of adult neural stem cells (NSCs) isolated from the substantia nigra and the subependymal zone (SEZ) stem cell niche to further characterize the effects of BNN-20. * Correspondence: [email protected]; [email protected]; [email protected] †Dimitrios Dimitrakopoulos and Dimitrios Kakogiannis contributed equally to this work. -
Age-Related Change in 5-HT6 Receptor Availability in Healthy Male Volunteers Measured with 11C-GSK215083 PET
BRIEF COMMUNICATION Age-Related Change in 5-HT6 Receptor Availability in Healthy Male Volunteers Measured with 11C-GSK215083 PET Rajiv Radhakrishnan1, Nabeel Nabulsi2, Edward Gaiser1, Jean-Dominique Gallezot2, Shannan Henry2, Beata Planeta2, Shu-fei Lin2, Jim Ropchan2, Wendol Williams1, Evan Morris2,3, Deepak Cyril D’Souza1, Yiyun Huang2, Richard E. Carson2,3, and David Matuskey1,2 1Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut; 2Department of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, Connecticut; and 3Department of Biomedical Engineering, Yale University, New Haven, Connecticut because it presents an attractive therapeutic target for neuropsychi- Serotonin receptor 6 (5-hydroxytrypamine-6, or 5-HT6) is a potential atric disorders. therapeutic target given its distribution in brain regions that are Functionally, 5-HT6 exhibits excitatory action, but it can also important in depression, anxiety, and cognition. This study sought colocalize with g-aminobutyric acid–ergic neurons and produce an to investigate the effects of age on 5-HT6 receptor availability using inhibition of brain activity leading to complicated and discrepant 11 C-GSK215083, a PET ligand with affinity for 5-HT6 in the striatum results (2,4). Heterogeneous effects are also seen with other neu- and 5-HT in the cortex. Methods: Twenty-eight healthy male vol- 2A rotransmitters in specific brain regions, with 5-HT antagonism unteers (age range, 23–52 y) were scanned with 11C-GSK215083 6 PET. Time–activity curves in regions of interest were fitted using a resulting in increased extracellular glutamate, dopamine, and ace- multilinear analysis method. Nondisplaceable binding potential tylcholine in the frontal cortex and hippocampus (5,6), whereas (BPND) was calculated using the cerebellum as the reference region 5-HT6 agonists have been shown to produce increased extracellu- and corrected for partial-volume effects. -
Dopaminergic Microtransplants Into the Substantia Nigra of Neonatal Rats with Bilateral 6-OHDA Lesions
The Journal of Neuroscience, May 1995, 15(5): 3548-3561 Dopaminergic Microtransplants into the Substantia Nigra of Neonatal Rats with Bilateral 6-OHDA Lesions. I. Evidence for Anatomical Reconstruction of the Nigrostriatal Pathway Guido Nikkhah,1,2 Miles G. Cunningham,3 Maria A. Cenci,’ Ronald D. McKay,4 and Anders Bj6rklund’ ‘Department of Medical Cell Research, University of Lund, S-223 62 Lund, Sweden, *Neurosurgical Clinic, Nordstadt Hospital, D-301 67 Hannover, Germany, 3Harvard Medical School, Boston, Massachusetts 02115, and 4 Laboratory of Molecular Biology, NINDS NIH, Bethesda, Maryland 20892 Reconstruction of the nigrostriatal pathway by long axon [Key words: target reinnervation, axon growth, neural growth derived from dopamine-rich ventral mesencephalic transplantation, tyrosine hydroxylase immunohistochem- (VM) transplants grafted into the substantia nigra may en- istry, Fos protein, Fluoro-Gold] hance their functional integration as compared to VM grafts implanted ectopically into the striatum. Here we report on In the lesioned brain of adult recipients dopamine-rich grafts a novel approach by which fetal VM grafts are implanted from fetal ventral mesencephalon (VM) are unable to reinner- unilaterally into the substantia nigra (SN) of 6-hydroxydo- vate the caudate-putamen unless they are placed close to, or pamine (SOHDA)-lesioned neonatal pups at postnatal day within, the denervated target structure (BjGrklund et al., 1983b; 3 (P3) using a microtransplantation technique. The results Nikkhah et al., 1994b). The failure of regenerating dopaminergic demonstrate that homotopically placed dopaminergic neu- axons to reinnervate the striatum from more distant implantation rons survive and integrate well into the previously sites, including their normal site of origin, the substantia nigra 6-OHDA-lesioned neonatal SN region. -
The Significance of NK1 Receptor Ligands and Their Application In
pharmaceutics Review The Significance of NK1 Receptor Ligands and Their Application in Targeted Radionuclide Tumour Therapy Agnieszka Majkowska-Pilip * , Paweł Krzysztof Halik and Ewa Gniazdowska Centre of Radiochemistry and Nuclear Chemistry, Institute of Nuclear Chemistry and Technology, Dorodna 16, 03-195 Warsaw, Poland * Correspondence: [email protected]; Tel.: +48-22-504-10-11 Received: 7 June 2019; Accepted: 16 August 2019; Published: 1 September 2019 Abstract: To date, our understanding of the Substance P (SP) and neurokinin 1 receptor (NK1R) system shows intricate relations between human physiology and disease occurrence or progression. Within the oncological field, overexpression of NK1R and this SP/NK1R system have been implicated in cancer cell progression and poor overall prognosis. This review focuses on providing an update on the current state of knowledge around the wide spectrum of NK1R ligands and applications of radioligands as radiopharmaceuticals. In this review, data concerning both the chemical and biological aspects of peptide and nonpeptide ligands as agonists or antagonists in classical and nuclear medicine, are presented and discussed. However, the research presented here is primarily focused on NK1R nonpeptide antagonistic ligands and the potential application of SP/NK1R system in targeted radionuclide tumour therapy. Keywords: neurokinin 1 receptor; Substance P; SP analogues; NK1R antagonists; targeted therapy; radioligands; tumour therapy; PET imaging 1. Introduction Neurokinin 1 receptor (NK1R), also known as tachykinin receptor 1 (TACR1), belongs to the tachykinin receptor subfamily of G protein-coupled receptors (GPCRs), also called seven-transmembrane domain receptors (Figure1)[ 1–3]. The human NK1 receptor structure [4] is available in Protein Data Bank (6E59). -
Striatal and Midbrain Connectivity with the Hippocampus Selectively Boosts Memory for Contextual Novelty
HIPPOCAMPUS 25:1262–1273 (2015) Striatal and Midbrain Connectivity with the Hippocampus Selectively Boosts Memory for Contextual Novelty Alexandros Kafkas* and Daniela Montaldi ABSTRACT: The role of contextual expectation in processing familiar of the new information (Kakade and Dayan, 2002). and novel stimuli was investigated in a series of experiments combining eye The ability to discriminate potentially salient familiar tracking, functional magnetic resonance imaging, and behavioral methods. An experimental paradigm emphasizing either familiarity or novelty detec- and novel information, in a context abundant with tion at retrieval was used. The detection of unexpected familiar and novel old and new stimuli, becomes crucial for ensuring stimuli, which were characterized by lower probability, engaged activity in effective contextual learning. Efficient discrimination midbrain and striatal structures. Specifically, detecting unexpected novel may trigger an orienting response toward the new stimuli, relative to expected novel stimuli, produced greater activity in the unexpected information and may therefore enhance substantia nigra/ventral tegmental area (SN/VTA), whereas the detection of unexpected familiar, relative to expected, familiar stimuli, elicited activity memory formation (Tulving and Kroll, 1995). Indeed, in the striatum/globus pallidus (GP). An effective connectivity analysis the brain’s dopaminergic system, including striatal and showed greater functional coupling between these two seed areas (GP and midbrain structures, has been shown to respond to SN/VTA) and the hippocampus, for unexpected than for expected stimuli. reward anticipation and to prediction errors as well as Within this network of midbrain/striatal–hippocampal interactions two having an effect on memory formation (Adcock et al., pathways are apparent; the direct SN–hippocampal pathway sensitive to unexpected novelty and the perirhinal–GP–hippocampal pathway sensitive 2006; Wittmann et al., 2011). -
Issues Surrounding the Cognitive Neuroscience of Obsessive-Compulsive Disorder
Psychonomic Bulletin & Review 1998,5(2),161-172 Issues surrounding the cognitive neuroscience of obsessive-compulsive disorder KEVIN D. WILSON University ofPennsylvania, Philadelphia, Pennsylvania Obsessive-compulsive disorder (OCD) has been studied extensively in recent years, with increased emphasis on understanding OCD's biological substrates. There has been significant progress in docu menting abnormal brain function in OCD patients, particularly in the orbitofrontal cortex, basal gan glia, and thalamus. Similar progress has broadened our understanding of the cognitive and behavioral manifestations ofthe disorder, including deficits in set shifting, hyperattention, and visuospatial con struction abilities. Unfortunately, these results have not been replicated consistently. This report com prises a review of previous attempts to characterize the neurobiology and neuropsychology of OCD, and a discussion ofseveral factors in OCD research that can help to explain previous inconsistencies. Obsessive-compulsive disorder (OCD) is a relatively logical features ofOCD. Only then will an adequate the common form ofpsychopathology with a lifetime preva ory ofthe cognitive neuroscience ofOCD be possible. lence of2%-3% (Robins et al., 1984). Although the ana tomical and behavioral regularities of the disorder have PHENOMENOLOGY OF OeD been studied extensively over the past 20 years, there has been relatively little success in the attempt to establish OCD is grouped under the general heading ofanxiety how the former give rise to the latter. Popular models of disorders. The DSM-IV(American Psychological Asso OCD have drawn upon a variety ofdisciplines, including ciation, 1994) defines OCD as "recurrent obsessions or learning theory (Mowrer, 1960), cybernetics (Pitman, compulsions that are severe enough to be time consum 1987) and psychoanalysis (Fenichel, 1945). -
MR Findings in Patients with Subacute Necrotizing Encephalomyelopathy (Leigh Syndrome): Correlation with Biochemical Defect
379 MR Findings in Patients with Subacute Necrotizing Encephalomyelopathy (Leigh Syndrome): Correlation with Biochemical Defect 1 2 L. Medina · MR studies were correlated with biochemical results in nine children who presented 1 3 T. L. Chi · with lactic acidosis andjor abnormal MR findings in the basal ganglia. Neurologic D. C. DeVivo4 development was delayed in all nine children. Seven of these patients were diagnosed S. K. Hilal 1 as having subacute necrotizing encephalomyelopathy (SNE, or Leigh syndrome) on the basis of history, clinical findings, and biochemical studies; of the remaining two, one had congenital lactic acidosis and the other had familial bilateral striatal necrosis with no known biochemical correlate. Although the clinical presentation of these patients was similar, we found distinctive MR abnormalities in characteristic locations in the seven patients with SNE, with or without detectable specific mitochondrial enzyme deficiency in cultured skin fibroblast assays. In our case studies of SNE patients with detectable enzyme deficiency states, defects in pyruvate dehydrogenase complex and cytochrome c oxidase have been found. The MR finding of note in SNE is the remarkably symmetrical involvement, most frequently of the putamen. In our study, lesions were also commonly found in the globus pallidus and the caudate nucleus, but never in the absence of putamina! abnormalities. Other areas of involvement included the paraven tricular white matter, corpus callosum, substantia nigra, decussation of superior cere bellar peduncles, periaqueductal region, and brainstem. In patients who present with lactic acidosis and whose MR findings show symmetrical abnormalities in the brain, but with sparing of the putamen, the diagnosis of SNE is in doubt. -
Focused Ultrasound Enhanced Intranasal Delivery of Brain Derived
www.nature.com/scientificreports OPEN Focused ultrasound enhanced intranasal delivery of brain derived neurotrophic factor produces neurorestorative efects in a Parkinson’s disease mouse model Robin Ji 1, Morgan Smith1, Yusuke Niimi1, Maria E. Karakatsani 1, Maria F. Murillo1, Vernice Jackson-Lewis3,5,6, Serge Przedborski3,4,5,6 & Elisa E. Konofagou1,2* Focused ultrasound-enhanced intranasal (IN + FUS) delivery is a noninvasive approach that utilizes the olfactory pathway to administer pharmacological agents directly to the brain, allowing for a more homogenous distribution in targeted locations compared to IN delivery alone. However, whether such a strategy has therapeutic values, especially in neurodegenerative disorders such as Parkinson’s disease (PD), remains to be established. Herein, we evaluated whether the expression of tyrosine hydroxylase (TH), the rate limiting enzyme in dopamine catalysis, could be enhanced by IN + FUS delivery of brain-derived neurotrophic factor (BDNF) in a toxin-based PD mouse model. Mice were put on the subacute dosing regimen of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), producing bilateral degeneration of the nigrostriatal pathway consistent with early-stage PD. MPTP mice then received BDNF intranasally followed by multiple unilateral FUS-induced blood-brain barrier (BBB) openings in the left basal ganglia for three consecutive weeks. Subsequently, mice were survived for two months and were evaluated morphologically and behaviorally to determine the integrity of their nigrostriatal dopaminergic pathways. Mice receiving IN + FUS had signifcantly increased TH immunoreactivity in the treated hemisphere compared to the untreated hemisphere while mice receiving only FUS-induced BBB opening or no treatment at all did not show any diferences.