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Antagonistic properties of caged GABA compounds used for activation of GABAA receptors in neocortical pyramidal neurons

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dc.date.accessioned 2019-06-28T07:15:29Z
dc.date.available 2019-06-28T07:15:29Z
dc.date.issued 2019-06-28
dc.identifier.uri http://hdl.handle.net/123456789/24796
dc.title Antagonistic properties of caged GABA compounds used for activation of GABAA receptors in neocortical pyramidal neurons en
ethesis.discipline.URI none
ethesis.faculty Bio- ja ympäristötieteellinen tiedekunta fi
ethesis.faculty Faculty of Biological and Environmental Sciences en
ethesis.faculty Bio- och miljövetenskapliga fakulteten sv
ethesis.faculty.URI http://data.hulib.helsinki.fi/id/4d959249-d6aa-44fa-93ff-807dbf9ffaae
ethesis.university.URI http://data.hulib.helsinki.fi/id/50ae46d8-7ba9-4821-877c-c994c78b0d97
ethesis.university Helsingin yliopisto fi
ethesis.university University of Helsinki en
ethesis.university Helsingfors universitet sv
dct.creator Srinivasan, Rakenduvadhana
dct.issued 2019
dct.language.ISO639-2 eng
dct.abstract Caged photolysable compounds have served to be pivotal to neuroscientific investigations; allowing the cognizing of molecular kinetics and properties of neuronal micro-machinery such as neurotransmitter receptors. Precision in terms of temporal and spatial resolution of neurotransmitter release endowed by photolysis has multitudinal applicabilities in the realm of GABAA receptors (GABAARs), their neuronal niche and effects on neuronal and network activity. Caged compounds, in their caged form, may display certain unideal traits such as undesired interactions with the system and antagonistic activity on the target receptor. This study aims to reevaluate the GABAAR antagonistic actions of caged Rubi-GABA, which was found to antagonize these receptors at significantly lower concentrations than those reported in the literature. Furthermore, this study electrophysiologically characterizes the possible antagonistic properties of a novel quinoline-derived UV-photolysable caged GABA compound, 8 DMAQ GABA, whose activity, in its caged form appears to have a much more favorable antagonism profile compared to the widely used RuBi-GABA. To assess the antagonistic effects of these compounds on GABAAR-mediated miniature inhibitory postsynaptic currents (mIPSCs) patch-clamp recordings were carried out in the whole-cell voltage clamp configuration on cortical layer 2/3 cortical pyramidal neurons in acute neocortical slices prepared from 16-18 day-old rat rats. The results of this study indicate a revised antagonism profile for caged Rubi-GABA, with marked GABAAR toxicity in the low micromolar range. The study also scrutinizes the photo-kinetic properties of both caged GABA compounds and reveals that the rate of GABA release from 8-DMAQ is slower than from RuBi-GABA. en
dct.subject Caged GABA en
dct.subject GABAA Receptors en
dct.subject Antagonism en
dct.subject Photo-activation en
dct.subject Neurotransmitter en
dct.subject Electrophysiology en
dct.subject RuBi-GABA en
dct.subject 8-DMAQ GABA en
dct.language en
ethesis.language.URI http://data.hulib.helsinki.fi/id/languages/eng
ethesis.language englanti fi
ethesis.language English en
ethesis.language engelska sv
ethesis.supervisor Puskarjov, Martin
ethesis.supervisor Kaila, Kai
ethesis.thesistype pro gradu -tutkielmat fi
ethesis.thesistype master's thesis en
ethesis.thesistype pro gradu-avhandlingar sv
ethesis.thesistype.URI http://data.hulib.helsinki.fi/id/thesistypes/mastersthesis
dct.identifier.ethesis E-thesisID:d234354d-4b0e-471e-86f6-6942d7adf8af
ethesis-internal.timestamp.reviewStep 2019-06-13 12:32:23:212
ethesis.principalprofessor Voipio, Juha
ethesis.principalprofessor Kaila, Kai
dct.identifier.urn URN:NBN:fi:hulib-201906283087
dc.type.dcmitype Text
ethesis.facultystudyline Neurotiede fi
ethesis.facultystudyline Neuroscience en
ethesis.facultystudyline Neurovetenskap sv
ethesis.facultystudyline.URI http://data.hulib.helsinki.fi/id/SH57_128
ethesis.mastersdegreeprogram Neurotieteiden maisteriohjelma fi
ethesis.mastersdegreeprogram Master's Programme in Neuroscience en
ethesis.mastersdegreeprogram Magisterprogrammet i neurovetenskap sv
ethesis.mastersdegreeprogram.URI http://data.hulib.helsinki.fi/id/MH57_004

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