acase@tulane.edu / The lack of Short Stature Homeobox Gene, SHOX, caused several symptoms in humans including the short stature, skeletal abnormalities, heart diseases and cognitive problems. To understand the role of SHOX and SHOX2 in humans, the study of homolog gene Shox2 in mice has been applied. Previous researches have revealed that Shox2 has important role in bone, palate, heart and hindbrain development. Especially, Shox2 is critical for the development of heart pacemaker cells. In this dissertation, we studied the role of Shox2 in the thalamus of young adult mice. Our results indicated that Shox2 expression during development in the forebrain is relatively limited in the thalamus. To study the role of Shox2 in thalamic properties and functions, we conducted tamoxifen inducible knock out (KO) in RosaCreERt/+, Shox2f/f mice. Our behavioral studied showed that Shox2 KO impairs mice total activity, somatosensory function and learning and memory process, suggesting Shox2 is critical for thalamus-related behaviors. To investigate the underlying mechanism, we conducted electrophysiological experiment to test physiological properties of thalamic neurons. Our results showed that Shox2 KO caused changes in intrinsic properties including decreased cell excitability. Besides, our TUNEL staining results revealed Shox2 inducible KO in midline thalamus οf Gbx2CreERt/+, Shox2f/f mice caused increased cell death in the midline thalamus. We further investigate whether pacemaking related ion channels are involved in cellular properties impairments caused by Shox2 KO. The following experiments revealed a decrease in mRNA and protein expression of Cav3.1 and T-type calcium current density, and in mRNA and protein expression of HCN2 and HCN4 channels and HCN current. The similar enriched genes related to T-type calcium and HCN channels with heart pacemaker cells and the specific down-regulation of these genes by Shox2 KO suggested the critical role of Shox2 in maintenance of thalamic pacemaking properties and behavioral functions. Our mRNA sequencing results indicated that enriched differently expressed genes (DEGs) in gene ontology (GO) terms of cell death, neuron projection development and response to stimulus between CR and KO samples and thalamus specifically enriched genes are highly regulated by Shox2 KO, suggesting Shox2 is important for thalamic identity and survival. / 1 / Diankun Yu

Thesis (doctor of medicine)--Rijksuniversiteit to Groningen, 1969.

Thesis (doctor of medicine)--Rijksuniversiteit to Groningen, 1969.

<p><strong> </strong></p><p><strong>Abstract</strong></p><p>The purpose of this thesis is to examine the electrical properties of pacemaker leads by measurements and theoretical analysis.</p><p>If time allows, recommendations on how to construct a simple circuit model to explain the phenomenon will be given based on the electrical properties obtained from measurements performed during the work of this thesis. Additional information on pacemaker lead heating during impact of magnet in X-ray (MRI) will be presented if time allows. Significant electrical properties of pacemaker leads are compiled in this thesis.</p><p> </p><p>ANALYSIS OF CIRCUIT MODEL</p><p>The purpose of this model is to create an equivalent electronic circuit model that describes a pacemaker lead electrical property. The model is divided into three different sections: proximal part, the homogeneous coil part and the distal end.  The model will include series inductance, parallel capacitance, series resistance, lossless admittance and winding capacitance between each loop for the homogeneous coil part, additionally the impedance of the proximal and distal part will be included.</p>

Abstract The purpose of this thesis is to examine the electrical properties of pacemaker leads by measurements and theoretical analysis. If time allows, recommendations on how to construct a simple circuit model to explain the phenomenon will be given based on the electrical properties obtained from measurements performed during the work of this thesis. Additional information on pacemaker lead heating during impact of magnet in X-ray (MRI) will be presented if time allows. Significant electrical properties of pacemaker leads are compiled in this thesis.   ANALYSIS OF CIRCUIT MODEL The purpose of this model is to create an equivalent electronic circuit model that describes a pacemaker lead electrical property. The model is divided into three different sections: proximal part, the homogeneous coil part and the distal end.  The model will include series inductance, parallel capacitance, series resistance, lossless admittance and winding capacitance between each loop for the homogeneous coil part, additionally the impedance of the proximal and distal part will be included.

Thesis (doctoral)--Ludwig Maximilians-Universität zu München, 1979.

Thesis (doctoral)--Ludwig Maximilians-Universität zu München, 1979.

Les pathologies du nœud sino-atrial provoquent un dysfonctionnement intrinsèque de l'automaticité de ce tissu. La maladie, l'âge ou une anomalie génétique peuvent être la cause d'un dérèglement de la fréquence cardiaque associé à la bradycardie ou la dysfonction atrio-ventriculire. Sans intervention médicale cette pathologie peut conduire à l'arrêt cardiaque. Les pathologies touchant le sinus sont fréquentes, avec une occurrence accrue dans la population âgée. Ainsi, avec le vieillissement des populations occidentales il devient primordial de mieux comprendre les mécanismes générant l'activité automatique du cœur. Les nombreuses études déjà réalisées dans ce domaine ont conduit à une forte controverse entre deux modèles explicatifs des mécanismes pacemaker. Dans ce contexte, j'ai étudié au cours de cette thèse le rôle joué par les canaux calciques Cav1.3 dans la génération de l'activité pacemaker. Afin de distinguer et expliquer le rôle des différents canaux ioniques impliqués dans le mécanisme pacemaker nous avons utilisé une combinaison d'outils pharmacologiques et plusieurs souches de souris transgéniques dont les gènes impliqués dans l'activité pacemaker étaient inactivés ou leur fonction modifiée. Dans le but de constituer un nouveau cadre d'interprétation du mécanisme pacemaker, plusieurs approches expérimentales ont été utilisées. L'activité pacemaker a été étudié dans 3 systèmes au niveau de complexité croissant: des cellules sino-atriales isolées, des tissus sino-atriales entiers et des animaux vivants. Ces différentes approches ont permis d'obtenir des résultats probants et ouvrent la voie à une meilleure compréhension de l'automaticité. En conclusion de cette thèse, nous proposons un cadre intégratif des modèles préexistants, dans lequel les canaux de la membrane cytoplasmique et les libérations de calcium interagissent pour générer un mécanisme pacemaker complexe. / The “sick sinus syndrome” has been defined as an intrinsic dysfunction of the heart Sino-atrial node to perform its pacemaking function. Disease, ageing, or gene defects may cause sinus dysfunctions, ranging from rhythm disturbance to bradycardia, sinus pauses, sinus arrest, and arrhythmias. Without medical intervention these dysfunctions can result in heart block. Sick sinus syndrome is a common pathology, with an increased penetration in the elder population. In the light of the actual increase of elderly in western population, a better comprehension of the mechanism generating spontaneous automaticity appears fundamental. Several investigations have been already carried out in the field of automaticity, leading to a heated controversy between two models of the pacemaker mechanism. In the light this controversy, we investigated the role of Ca2+ channels in generating pacemaker activity. In order to discern and explain the roles of different ion channel actors already implicated in the complex pacemaker machinery we used a combination of pharmacological tools and a variety of transgenic mice. These mice present genetic inactivation or modification in genes involved in pacemaker activity. Furthermore, to provide a new framework for interpreting the pacemaker mechanism, different experimental approaches have been employed. Pacemaker activity was studied in three systems with increasing complexity: isolated sino-atrial cells, intact sino-atrial tissues and in freely-moving animals. These systems led us to consistent conclusions and will pave the way to a better understanding of pacemaking. In particular, we propose an integrative framework for bridging current models in a common mechanism where both, membrane channels and Ca2+ release interact generating a complex pacemaker machinery.

Suprachiasmatic nuclei (SCN) are primary center of mammalian circadian rhythms. To maintain a 24 hour period of its rhythms, SCN are synchronized with phase of external environment. Regular changes of light and darkness are known to be the main external synchronizer that determines the period of SCN rhythms. Information about light is being transferred from retina to the ventrolateral region of SCN through excitatory synapses where ionotropic glutamate receptors (iGluRs) play a primary role in the signal transduction. Posttranscriptional modifications of RNA can alter the functional properties of iGluRs, thus this process contributes to synaptic plasticity. The extent of posttranscriptional modifications of iGluRs can be in vitro affected by neuronal activity altered by pharmacological manipulation. The aim of this study was to determine possible changes of posttranscriptional modifications of iGluRs in in vivo rat SCN model and how this process can be regulated. RNA posttranscriptional modifications of GluA2 subunit of AMPA receptor (AMPAR) and GluK2 subunit of kainate receptor were assessed using PCR and subsequent sequencing of amplified DNA. Using quantitative PCR, we also determined mRNA expression of GluA1 and GluA2 subunits of AMPAR and the editing enzyme ADAR2 in SCN. Our results showed...

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