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      Mammal-Like Striatal Functions in Anolis

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          Abstract

          Serotonin (5-HT) 5-HT<sub>2A</sub> and 5-HT<sub>2C</sub> receptors are thought to play important roles in the mammalian striatum. As basal ganglia functions in general are thought highly conserved among amniotes, we decided to use in situ autoradiographic methods to determine the occurrence and distribution of pharmacologically mammal-like 5-HT<sub>2A</sub> and 5-HT<sub>2C</sub> receptors in the lizard, Anolis carolinensis, with particular attention to the striatum. We also determined the distributions of 5-HT<sub>1A</sub>, 5-HT<sub>1B/D</sub>, 5 HT<sub>3</sub>, and 5-HT<sub>uptake</sub> receptors for comparison. All 5-HT receptors examined showed pharmacological binding specificity, and forebrain binding density distributions that resembled those reported for mammals. Anolis 5 HT<sub>2A/C</sub> and 5-HT<sub>1A</sub> site distributions were similar in both in vivo and ex vivo binding experiments. 5-HT<sub>2A & C</sub> receptors occur in both high and low affinity states, the former having preferential affinity for <sup>125</sup>I-(±)-2,5-dimethoxy-4-iodo-amphetamine hydrochloride (<sup>125</sup>I-DOI). In mammals <sup>125</sup>I-DOI binding shows a patchy density distribution in the striatum, being more dense in striosomes than in surrounding matrix. There was no evidence of any such patchy density of <sup>125</sup>I-DOI binding in the anole striatum, however. As a further indication that anoles do not possess a striosome and matrix striatal organization, neither <sup>3</sup>H-naloxone binding nor histochemical staining for acetylcholinesterase activity (AChE) were patchy. AChE did show a band-like striatal distribution, however, similar to that seen in birds.

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          The organization of the basal ganglia-thalamocortical circuits: open interconnected rather than closed segregated.

          Anatomical findings in primates and rodents have led to a description of several parallel segregated basal ganglia-thalamocortical circuits leading from a distinct frontocortical area, via separate regions in the basal ganglia and the thalamus, back to the frontocortical area from which the circuit originates. One of the questions raised by the concept of parallelism is whether and how the different circuits interact. The present Commentary proposes that interaction is inherent in the neural architecture of the basal ganglia-thalamocortical circuits. This proposal is based on the re-examination of the data on the topographical organization of the frontocortical-basal ganglia connections which indicates that each circuit-engaged striatal region sends divergent projections to parts of both substantia nigra pars reticulata and the internal segment of the globus pallidus (each ventral striatal region sends divergent projections to parts of ventral pallidum, substantia nigra pars reticulata and globus pallidus), and this segregation is maintained at subsequent thalamic and frontocortical levels. This results in an asymmetry in the frontal cortex-basal ganglia relationships, so that while each frontocortical subfield innervates one striatal region, each striatal region influences the basal ganglia output to two frontocortical subfields. Because of this asymmetry, at least one of the frontocortical targets of a given circuit-engaged striatal region is not the source of its frontocortical input. Since this organization is inconsistent with an arrangement in closed segregated circuits we introduce the concept of a "split circuit". A split circuit emanates from one frontocortical area, but terminates in two frontocortical areas. Thus, a split circuit contains at least one "open" striato-fronto-cortical pathway, that leads from a circuit-engaged striatal region to a frontocortical area which is a source of a different circuit. In this manner split circuits are interconnected via their open pathways. The second striato-fronto-cortical pathway of a split circuit can be another open pathway, or it can re-enter the frontocortical area of origin, forming a closed circuit. On the basis of the available anatomical data we tentatively identified a motor, an associative, and a limbic split circuit, each containing a closed circuit and an open pathway. The motor split circuit contains a closed motor circuit that re-enters the motor and premotor cortical areas and an open motor pathway that terminates in the associative prefrontal cortex. The associative split circuit contains a closed associative circuit that re-enters the associative prefrontal cortex and an open associative pathway that terminates in the premotor cortex.(ABSTRACT TRUNCATED AT 400 WORDS)
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            Pattern of expression of the serotonin2C receptor messenger RNA in the basal ganglia of adult rats.

            The distribution of the serotonin (5-HT) receptor 5-HT2C mRNA was examined at the single-cell level with in situ hybridization histochemistry and emulsion autoradiography in the basal ganglia and mesolimbic system of adult rats, with focus on the pallidum and the substantia nigra, which receive striatal inputs and play a critical role in basal ganglia function. 5-HT2C receptor mRNA expression was always restricted to a subpopulation of neurons in the regions examined. In the neostriatum, labeled neurons were more numerous in the rostral nucleus accumbens than in the caudal nucleus accumbens and were more numerous in the ventral and ventrolateral caudate-putamen than in the dorsal caudate-putamen, where labeled neurons were restricted to isolated clusters. In striatal target areas, dense labeling in the entopeduncular nucleus (internal pallidum, direct striatal output pathway) contrasted with an absence of labeling in the globus pallidus (external pallidum, indirect striatal output pathway). Double-label in situ hybridization in the substantia nigra revealed coexpression of 5-HT2C receptor mRNA with glutamic acid decarboxylase but not with tyrosine hydroxylase mRNA, indicating that it was restricted to gamma-aminobutyric acid (GABA)ergic neurons. In this region, dense labeling for 5-HT2C mRNA was found in half of the neurons at middle and caudal levels of both the pars compacta and the pars reticulata, with little labeling rostrally. The data suggest that drugs acting on the 5-HT2C receptor could selectively affect discrete neuronal populations in the basal ganglia and mesolimbic systems and indicate a new level of neurochemical heterogeneity among GABAergic neurons of the substantia nigra.
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              5-Hydroxytryptamine receptor subtypes in vertebrates and invertebrates.

              In the last few years, molecular biology has led to the cloning and characterization of several 5-HT receptors (serotonin receptors) in vertebrates and in invertebrates. These studies have allowed identification not only of 5-HT receptors already described but also of novel subtypes. The molecular cloning of 13 different mammalian receptor subtypes revealed an unexpected heterogeneity among 5-HT receptors. Except for the 5-HT3 receptors which are ligand-gated ion channel receptors, all the other 5-HT receptors belong to the large family of receptors interacting with G proteins. Based on their amino acid sequence homology and coupling to second messengers these receptors can be divided into distinct families: the 5-HT1 family contains receptors that are negatively coupled to adenylate cyclase: the 5-HT2 family includes receptors that stimulate phospholipase C; the adenylyl cyclase stimulatory receptors are a heterogeneous group including the 5-HT4 receptor which has not yet been cloned, the Drosophila 5-HTdro1 receptor and two mammalian receptors tentatively named 5-HT6 and 5-HT7 receptors. The 5-HT5A and 5-HT5B receptors might constitute a new family of 5-HT receptors whose effectors are unknown. This review focusses on the molecular characteristics of the cloned 5-HT receptors such as their structure, their effector systems and their distribution within the central nervous system. The existence of a large number of receptors with distinct signalling properties and expression patterns might enable a single substance like 5-HT to generate simultaneously a large panel of effects in many brain structures. The availability of the genes encoding these receptors has already allowed a partial characterization of their structure-function relationship and will probably allow in the future a dissection of the contribution of each of these receptor subtypes to physiology and behaviour.
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                Author and article information

                Journal
                BBE
                Brain Behav Evol
                10.1159/issn.0006-8977
                Brain, Behavior and Evolution
                S. Karger AG
                0006-8977
                1421-9743
                2000
                November 2000
                21 February 2001
                : 56
                : 5
                : 235-248
                Affiliations
                Departments of aPsychiatry and Behavioral Neurobiology, bPsychology, cNeurobiology, University of Alabama at Birmingham, Ala., dDepartments of Psychiatry, Pharmacology, the Laboratory of Nuclear Medicine of the UCLA DoE Laboratory of Structural Biology and Molecular Medicine, and the Crump Institute for Biomedical Imaging, University of California, Los Angeles, Calif., USA
                Article
                47207 Brain Behav Evol 2000;56:235–248
                10.1159/000047207
                11251316
                39068ab0-772e-4e94-a9ca-1d756484bd96
                © 2001 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                Page count
                Figures: 5, Tables: 1, References: 84, Pages: 14
                Categories
                Original Paper

                Geriatric medicine,Neurology,Cardiovascular Medicine,Neurosciences,Clinical Psychology & Psychiatry,Public health
                Acetylcholinesterase,<italic>Anolis</italic>,Basal ganglia,Striosomes,Serotonin receptors,Naloxone

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