Molecular and functional neuroanatomy of mood disorder circuits

The ability to interpret and react to external stimuli is essential for survival. An organism has to be able to predict a favorable outcome, and, more importantly, a non-favorable one that could mean danger for life. The mammalian brain has developed a number of strategies to interpret external stimuli, to learn the value of a stimulus and to make decisions that promote wellbeing. The underlying neuronal networks are intricate and require numerous interactions in order to provide adequate flow of information. Consequently, slight imbalances in these networks can have disastrous results. In humans, for example, imbalances in monoaminergic neurotransmission can lead to the development of affective disorders like depression and anxiety or brain disorders like schizophrenia, Parkinson’s disease or addiction. The neurons involved in these mechanisms are being researched extensively, using a plethora of state of the art methods that examine neuronal activity, connectivity and precise action during behavior, just to name a few. The above-mentioned diseases are fairly common in the global population, a fact that shows how crucial it is to understand the underlying mechanisms and to develop adequate treatment. The aim of this thesis is to describe the molecular and neuroanatomical properties of neural circuits involved in reward and punishment prediction and decisionmaking. In chapter 1, I will describe the monoaminergic systems in the mouse brain, mainly focusing on the serotonergic and dopaminergic systems and their involvement in behavior and mood disorders. Chapter 2 reviews classical and current literature on the neural circuits that regulate reward and aversion, with the main focus on the basal ganglia, the habenular complex and the lateral hypothalamic area. Chapter 3 will describe the methodology used to research these circuits on which this thesis is based. More specifically, I will focus on the emergence of big scale single-cell (and single-nuclei) RNA sequencing and in situ hybridization techniques and data analysis. In paper 1, we examined the role of the lateral habenula in aversive behavior and the underlying network connections. A main focus lies on the glutamatergic projections from the lateral hypothalamic area that regulate lateral-habenula activity in fear and avoidance behavior. Molecular distinctions between glutamatergic neurons from neighboring Globus pallidus interna and lateral hypothalamus facilitate the identification of input to the LHb in aversive behavioral tasks. In paper 2, we identified spatial, striosomal and cell-type specific molecular properties of the mouse striatum. We were able to show molecular distinctions between patch, exopatch and matrix SPNs in the striatum. In addition, we reveal a new spatial map of the striatum and identified a unique SPN type that is independent of this aforementioned spatial code, direct or indirect pathway, or patch/exopatch/matrix characterizations. In paper 3, we show a molecular map of the entire span of the mouse brain with specific emphasis on the spatial distribution of gene expression. This map combines RNA-sequencing with spatial information using spatial transcriptomics. In paper 4, we used a novel two-virus retrograde tracing approach that enabled us to tag the nuclei of neurons sending monosynaptic projections. This allowed us to show the molecular composition of habenula and lateral hypothalamus neurons that directly target serotonergic neurons in the dorsal raphe nucleus and dopaminergic neurons in the ventral tegmental area. To conclude, genetic targeting of specific neurons is a valuable tool to unravel the exact function of a network. The studies included in this thesis provide new insight into the molecular and neuroanatomical properties of brain circuits involved in behavior. This allows for the identification of possible new genetic targets for behavioral research and ultimately, better understanding of underlying mechanisms

Fine root structure, dynamics and proportion in net primary production of Norway spruce forest ecosystem in relation to site conditions

http://www.ester.ee/record=b1310777*es

Comparative study of the electron- and positron-atom bremsstrahlung

Fully relativistic treatment of the electron-atom and positron-atom bremsstrahlung is reported. The calculation is based on the partial-wave expansion of the Dirac scattering states in an external atomic field. A comparison of the electron and positron bremsstrahlung is presented for the single and double differential cross sections and the Stokes parameters of the emitted photon. It is demonstrated that the electron-positron symmetry of the bremsstrahlung spectra, which is nearly exact in the nonrelativistic regime, is to a large extent removed by the relativistic effects

Röntgenpolarimetrie angewandt zur Untersuchung der Bremsstrahlung spinpolarisierter Elektronen

In der vorliegenden Arbeit wurden die Eigenschaften der linearen Polarisation der Elektron-Kern-Bremsstrahlung untersucht, die in Stößen von polarisierten Elektronen mit Festkörpertargets entsteht. Dazu wurde ein Experiment an der Quelle für polarisierte Elektronen SPIN der TU Darmstadt durchgeführt, bei der Elektronen mit einer kinetischen Energie von 100 keV zur Verfügung standen. Zur Untersuchung der Bremsstrahlung wurden Messreihen sowohl mit unpolarisierten Elektronen wie auch mit transversal und longitudinal spinpolarisierten Elektronenstrahlen vorgenommen. Die in den Stößen der Elektronen mit Gold- und Kohlenstofftargets unterschiedlicher Dicke emittierte Röntgenstrahlung wurde mit einem Si(Li)-Compton-Polarimeter unter zwei verschiedenen Beobachtungswinkeln aufgezeichnet. Dieser neuartige Detektor ermöglichte die Bestimmung sowohl des Grades der linearen Polarisation als auch der Orientierung des Polarisationsvektors der Bremsstrahlungsphotonen für Energien im Bereich zwischen 70 und 100 keV. Den Schwerpunkt der Datenauswertung bildete die Untersuchung des sogenannten Polarisationstransfers von der Spinpolarisation der Elektronen auf die Polarisationseigenschaften der freiwerdenden Röntgenphotonen. Dieser Transfer spiegelt sich in einer Rotation des Polarisationsvektors der Photonen und in einem erhöhten Grad der linearen Polarisation wider. Beide Effekte konnten bei einer Relativmessung der Bremsstrahlungseigenschaften zwischen den unpolarisierten und den transversal polarisierten Elektronen nachgewiesen werden. Der Vergleich der experimentellen Resultate mit vollständig relativistischen Rechnungen zeigt eine gute qualitative Übereinstimmung

Entwurfsoptimierung von selbst-adaptiven Wartungsmechanismen für software-intensive technische Systeme

Diese Arbeit stellt neuartige Konzepte zur effizienten Entscheidungsunterstützung in der Rekonfiguration software-intensiver technischer Systeme mit limitiertem Wartungszugriff vor. Entgegen rein redundanzorientierter Ansätze, basiert die verfolgte Methodik auf der prädiktiven Vorausberechnung adäquater Konfigurationsalternativen im relevanten Lösungsraum. Das Wissen über Konfigurationsbeziehung wird frühzeitig manifestiert und zur autarken kosteneffizienten Abwägung der Alternativen eingesetzt

Doppler-tuned Bragg Spectroscopy of Excited Levels in He-Like Uranium: a discussion of the uncertainty contributions

We present the uncertainty discussion of a recent experiment performed at the GSI storage ring ESR for the accurate energy measurement of the He-like uranium 1s2p3P2- 1s2s3S1 intra-shell transition. For this propose we used a Johann-type Bragg spectrometer that enables to obtain a relative energy measurement between the He-like uranium transition, about 4.51 keV, and a calibration x-ray source. As reference, we used the Ka fluorescence lines of zinc and the Li-like uranium 1s22p2P3/2 - 1 s22s 2S1/2 intra-shell transition from fast ions stored in the ESR. A comparison of the two different references, i.e., stationary and moving x-ray source, and a discussion of the experimental uncertainties is presented