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Publié par | ruprecht-karls-universitat_heidelberg |
Publié le | 01 janvier 2009 |
Nombre de lectures | 16 |
Langue | English |
Poids de l'ouvrage | 9 Mo |
Extrait
Dissertation
submitted to the
Combined Faculties for the Natural Sciences and for Mathematics
of the Ruperto‐Carola University of Heidelberg, Germany
for the degree of
Doctor of Natural Sciences
presented by
Diplom‐Biochemikerin Nadine Holter
born in Miltenberg
Oral‐examination: ______________
I
Development of
phasic and tonic inhibitory GABAergic currents
in mouse dentate gyrus
Referees: Prof. Dr. Hilmar Bading
Prof. Dr. Andreas Draguhn
II
The present thesis was prepared at the Institute for Physiology and Pathophysiology of the Ruperto‐
Carola University of Heidelberg from December 2005 to November 2008, the doctoral thesis
supervisor was Prof. Dr. Andreas Draguhn.
Danksagung
An dieser Stelle möchte ich allen danken, die zum Gelingen meiner Doktorarbeit beigetragen haben.
Mein Dank gilt im Besonderen:
Prof. Dr. Andreas Draguhn, meinem Doktorvater, für die Betreuung der vorliegenden Arbeit
und für intensive Diskussionen.
Prof. Dr. Hilmar Bading für die Begutachtung dieser Arbeit.
Prof. Dr. Hannah Monyer für die Aufnahme in das Graduiertenkolleg 791 und die damit
verbundene finanzielle, sowie ideelle Förderung. Catherine Munzig für die Unterstützung.
Allen Kollegen der Arbeitsgruppe Draguhn für ein einzigartiges Arbeitsumfeld. Besonders Dr.
Claus Bruehl und Nadine Zuber für die Hilfestellung.
Meiner Familie für das Vertrauen und die Unterstützung. Tobias für intensive abendliche
Diskussionen und ehrliche Kritik.
III
Declarations according to § 8 (3) b) and c) of the doctoral degree regulations:
a) I hereby declare that I have written the submitted dissertation myself and in this process
have used no other sources or materials than those expressly indicated,
b) I hereby declare that I have not applied to be examined at any other institution, nor have I
used the dissertation in this or any other form at any other institution as an examination
paper, nor submitted it to any other faculty as a dissertation.
……………………………………… …….…..………………....................
date signature
Project‐related publications:
Holter NI, Zuber N, Bruehl C, & Draguhn A (2007). Functional maturation of developing interneurons
in the molecular layer of mouse dentate gyrus. Brain Res 1186, 56‐64.
Holter NI, Zylla M, Zuber N & Draguhn A. Tonic GABAergic inhibition in maturing dentate granule
cells. In preparation.
Publication from another project:
Holter NI*, Grimm C*, Draguhn A, and Bruehl C (2008) Compensatory increase in P/Q‐calcium
current‐mediated synaptic transmission following chronic block of N‐type channels. Neusci
Lett, 442 (1), 44‐49.
* both authors contributed equally
IV
Abstract
The present thesis describes functional and morphological properties of interneurons and granule
cell in developing mouse dentate gyrus, with special focus on inhibitory GABAergic currents. The
dentate gyrus is the main hippocampal input structure receiving strong excitatory cortical afferents
via the perforant path. Therefore, inhibition at the ‘hippocampal gate’ is important, particularly
during postnatal development, when the hippocampal network is prone to seizures.
During this critical period of development the intrinsic and synaptic properties of developing
inhibitory interneurons were monitored in the molecular layer of mouse hippocampal slices. In this
region, mainly calretinin‐positive cells of multipolar appearance were found. These GABAergic
interneurons showed maturational changes of their intrinsic and synaptic properties after the first
postnatal week. The maturation of molecular layer interneurons went along with faster and larger
action potentials, increased repetitive firing, and increased frequency of spontaneous postsynaptic
inhibitory currents. All developmental changes in intrinsic and synaptic properties occurred between
postnatal day 6‐8 and postnatal day 9‐11, indicating a rapid functional maturation at the end of the
first postnatal week.
Age‐dependent changes of intrinsic and synaptic properties were also found in developing dentate
gyrus granule cells. Similar to interneurons, mature dentate gyrus granule cells exhibited faster and
larger action potentials and showed an increased frequency of spontaneous postsynaptic inhibitory
currents. Thus, the integration of granule cells in the inhibitory synaptic network of dentate gyrus
took place after the second postnatal week.
The data shows a rapid functional maturation of intrinsic and synaptic properties of interneurons and
granule cells in the dentate gyrus and an early integration into the synaptic networks. However,
stratum molecular interneurons were integrated prior to granule cells in the dentate gyrus network,
which is corresponding to their subsequent developmental appearance. <