United in Diversity: A Physiological and Molecular Characterization of Subpopulations in the Basal Ganglia Circuitry

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Viereckel, Thomas,1987-Uppsala universitet,Institutionen för neurovetenskap (author)

United in Diversity : A Physiological and Molecular Characterization of Subpopulations in the Basal Ganglia Circuitry

BookEnglish2017

Publisher, publication year, extent ...

Uppsala :Acta Universitatis Upsaliensis,2017
57 s.
electronicrdacarrier

Numbers

LIBRIS-ID:oai:DiVA.org:uu-328038
ISBN:9789151300634
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-328038URI

Supplementary language notes

Language:English
Summary in:English

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SwePubSwePub

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Subject category:vet swepub-contenttype
Subject category:dok swepub-publicationtype

Series

Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine,1651-6206 ;1369

Notes

The Basal Ganglia consist of a number of different nuclei that form a diverse circuitry of GABAergic, dopaminergic and glutamatergic neurons. This complex network is further organized in subcircuits that govern limbic and motor functions in humans and other vertebrates. Due to the interconnection of the individual structures, dysfunction in one area or cell population can affect the entire network, leading to synaptic and molecular alterations in the circuitry as a whole. The studies in this doctoral thesis aimed at characterizing restricted subpopulations of neurons in the Basal Ganglia circuitry and their importance in the wider function of the network. To this end, we identified subpopulations of neurons in the subthalamic nucleus (STN), substantia nigra (SN) and ventral tegmental area (VTA), characterized their molecular profile and investigated their physiological role in the circuitry.Within the mouse STN, reduction of glutamatergic neurotransmission in a subpopulation expressing Paired-like homeodomain transcription factor 2 (Pitx2) led to structural alterations in the nucleus as well as biochemical alterations of the dopaminergic system in the Nucleus accumbens (NAc) and changes in reward-related behavior. In the ventral midbrain, we identified and characterized novel marker genes selective to the VTA or SN. Of these, transient receptor potential cation channel subfamily V member 1 (TrpV1) marks a population of mainly glutamatergic neurons in the VTA which project to the NAc, while gastrin releasing peptide (Grp) is expressed in a population of dopaminergic neurons neuroprotected in Parkinson's disease. Furthermore, we discovered that disruption of glutamatergic co-release of dopaminergic neurons expressing dopamine transporter (DAT), diminishes fast EPSCs and glutamate release but does not affect the acquisition of reward-related behavioral tasks. To selectively quantify glutamate release from specific subpopulations, we devised a technique combining glutamate-amperometry and optogenetics. This was used to measure glutamate released from Pitx2-expressing synaptic terminals in the Globus pallidus as well as DAT- or TrpV1-expressing terminals in the NAc.In summary, this doctoral thesis has furthered understanding of the function and importance of specific subpopulations within the Basal Ganglia circuitry and provides a novel means to investigate glutamate in the intact rodent brain within clearly defined, restricted cell populations.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Neurovetenskaper hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Neurosciences hsv//eng
MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Fysiologi hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Physiology hsv//eng
TEKNIK OCH TEKNOLOGIER Medicinteknik Medicinsk laboratorie- och mätteknik hsv//swe
ENGINEERING AND TECHNOLOGY Medical Engineering Medical Laboratory and Measurements Technologies hsv//eng
Glutamate
Optogenetics
Amperometry
Histology
Midbrain
Subthalamic Nucleus
Parkinson's disease
Ventral Tegmental Area
Substantia Nigra
Co-release

Added entries (persons, corporate bodies, meetings, titles ...)

Wallén-Mackenzie, Åsa,ProfessorUppsala universitet,Jämförande fysiologi (thesis advisor)
Konradsson-Geuken, Åsa,DoktorUppsala universitet,Institutionen för farmaceutisk biovetenskap (thesis advisor)
Comasco, Erika,ProfessorUppsala universitet,Neuropsykofarmakologi (thesis advisor)
Svenningsson, Per,ProfessorKarolinska Institutet, Department of Clinical Neuroscience (opponent)
Uppsala universitetInstitutionen för neurovetenskap (creator_code:org_t)

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