Teilw. zugl.: Stockholm, Kungliga Tekniska högskolan, Diss., 2008. / Enth. außerdem Zeitschr.-Aufsätze des Verf.

In dieser Arbeit werden Quantenpunkt-Speichertransistoren basierend auf modulationsdotierten GaAs/AlGaAs Heterostrukturen mit vorpositionierten InAs Quantenpunkten vorgestellt, welche in Abhängigkeit der Ladung auf den Quantenpunkten unterschiedliche Widerstände und Kapazitäten aufweisen. Diese Ladungsabhängigkeiten führen beim Anlegen von periodischen Spannungen zu charakteristischen, durch den Ursprung gehenden Hysteresen in der Strom-Spannungs- und der Ladungs-Spannungs-Kennlinie. Die ladungsabhängigen Widerstände und Kapazitäten ermöglichen die Realisierung von neuromorphen Operationen durch Nachahmung von synaptischen Funktionalitäten und arithmetischen Operationen durch Integration von Spannungs- und Lichtpulsen. / In this thesis, state-dependent resistances and capacitances in quantum dot floating gate transistors based on modulation doped GaAs/AlGaAs heterostructures with site-controlled InAs quantum dots are presented. The accumulation of electrons in the quantum dots simultaneously increases the resistance and decreases the capacitance, which leads to characteristic pinched hysteresis loops in the current-voltage- and the charge-voltage-characteristics when applying periodic input signals. The concurrent resistance and capacitance switching enables the realization of neuromorphic operations via mimicking of synaptic functionalities and arithmetic operations via the integration of voltage and light pulses.

The analysis of microcircuitry (the connectivity at the level of individual neuronal processes and synapses), which is indispensable for our understanding of brain function, is based on serial transmission electron microscopy (TEM) or one of its modern variants. Due to technical limitations, most previous studies that used serial TEM recorded relatively small stacks of individual neurons. As a result, our knowledge of microcircuitry in any nervous system is very limited. We applied the software package TrakEM2 to reconstruct neuronal microcircuitry from TEM sections of a small brain, the early larval brain of Drosophila melanogaster. TrakEM2 enables us to embed the analysis of the TEM image volumes at the microcircuit level into a light microscopically derived neuro-anatomical framework, by registering confocal stacks containing sparsely labeled neural structures with the TEM image volume. We imaged two sets of serial TEM sections of the Drosophila first instar larval brain neuropile and one ventral nerve cord segment, and here report our first results pertaining to Drosophila brain microcircuitry. Terminal neurites fall into a small number of generic classes termed globular, varicose, axiform, and dendritiform. Globular and varicose neurites have large diameter segments that carry almost exclusively presynaptic sites. Dendritiform neurites are thin, highly branched processes that are almost exclusively postsynaptic. Due to the high branching density of dendritiform fibers and the fact that synapses are polyadic, neurites are highly interconnected even within small neuropile volumes. We describe the network motifs most frequently encountered in the Drosophila neuropile. Our study introduces an approach towards a comprehensive anatomical reconstruction of neuronal microcircuitry and delivers microcircuitry comparisons between vertebrate and insect neuropile.

The analysis of microcircuitry (the connectivity at the level of individual neuronal processes and synapses), which is indispensable for our understanding of brain function, is based on serial transmission electron microscopy (TEM) or one of its modern variants. Due to technical limitations, most previous studies that used serial TEM recorded relatively small stacks of individual neurons. As a result, our knowledge of microcircuitry in any nervous system is very limited. We applied the software package TrakEM2 to reconstruct neuronal microcircuitry from TEM sections of a small brain, the early larval brain of Drosophila melanogaster. TrakEM2 enables us to embed the analysis of the TEM image volumes at the microcircuit level into a light microscopically derived neuro-anatomical framework, by registering confocal stacks containing sparsely labeled neural structures with the TEM image volume. We imaged two sets of serial TEM sections of the Drosophila first instar larval brain neuropile and one ventral nerve cord segment, and here report our first results pertaining to Drosophila brain microcircuitry. Terminal neurites fall into a small number of generic classes termed globular, varicose, axiform, and dendritiform. Globular and varicose neurites have large diameter segments that carry almost exclusively presynaptic sites. Dendritiform neurites are thin, highly branched processes that are almost exclusively postsynaptic. Due to the high branching density of dendritiform fibers and the fact that synapses are polyadic, neurites are highly interconnected even within small neuropile volumes. We describe the network motifs most frequently encountered in the Drosophila neuropile. Our study introduces an approach towards a comprehensive anatomical reconstruction of neuronal microcircuitry and delivers microcircuitry comparisons between vertebrate and insect neuropile.

Das Ziel der kognitiven Neurowissenschaften ist es, Struktur-Funktions-Beziehungen im Gehirn aufzudecken. Durch Fortschritte in der funktionellen Bildgebung und der Graphentheorie konnten zentrale Knotenpunkte im Gehirn identifiziert werden, welche neuronale Informationen integrieren und dementielle Prozesse erklären können. Datenbankgetriebene metaanalytische Methoden wurden genutzt, um tausende Bildgebungsstudien auszuwerten und das funktionelle Profil von Hirnregionen zu dekodieren. Das Systems-Level Decoding zielt darauf ab, eine Seed-Region und mit ihr verbundene kortikale Regionen funktionell zu dekodieren. In Studie 1 wurden thalamische Subregionen und in Studie 2 drei Subregionen des Intraparietalen Sulcus (hIP) als Seed-Regionen verwendet. Studie 3 untersuchte Unterschiede in der Rich-Club-Struktur zwischen Alzheimer-Patienten, Patienten mit milder kognitiver Beeinträchtigung und gesunden Probanden. Es wurden zwei große, Thalamus-zentrierte Systeme identifiziert, die mit autobiographischem Gedächtnis und Nozizeption assoziiert sind; für den hIP wurden neun Systeme, die mit Prozessen wie Arbeitsgedächtnis und numerischem Denken zusammenhängen, gefunden. Studie 3 fand Hinweise, dass periphere Regionen bei Patienten im Vergleich zu gesunden Kontrollen stärker aktiviert sind als Rich-Club-Regionen. Das Systems-Level Decoding lieferte neue Erkenntnisse über die Einbettung des Thalamus und des hIP in kortikale funktionelle Systeme. Allerdings waren die Ergebnisse hinsichtlich der funktionellen Charakterisierung thalamischer Kerne und der Aktivitätsunterschiede in Rich-Club- und peripheren Regionen zwischen Patienten und gesunden Kontrollpersonen begrenzt. Diese Ergebnisse lassen sich möglicherweise durch Limitationen des metaanalytischen Ansatzes erklären. Das Systems-Level Decoding ist insgesamt ein vielversprechender Ansatz für die Formulierung von Hypothesen über Struktur-Funktionsbeziehungen innerhalb der Netzwerkarchitektur des menschlichen Gehirns. / In cognitive neuroscience, there is great interest in unraveling structure-function relationships in the human brain. Advances in functional neuroimaging and graph theory methods have identified key brain nodes relevant for neuronal information integration and functional deficits in degenerative diseases like Alzheimer's. Database-driven meta-analytical methods have also evaluated knowledge from thousands of neuroimaging studies, to decode the functional profile of brain regions. The systems-level decoding aims to identify brain systems that provide insight into the functional characteristics of a seed region and its connected cortical regions. In Study 1, thalamic subregions were used as seed regions. Study 2 applied systems-level decoding to three distinct regions in the intraparietal sulcus (hIP). In Study 3, we attempted to substantiate activation differences in the Rich Club structure between Alzheimer's patients, patients with mild cognitive impairment, and healthy subjects. Two major, thalamus-centered systems associated with autobiographical memory and nociception were identified. Additionally, nine large systems associated with processes such as working memory, numerical cognition, and recognition memory were uncovered for the hIP. Finally, evidence showed that peripheral regions in patients are more activated than central Rich Club regions compared to healthy controls. Systems-level decoding provided significant new insights into the embedding of the thalamus and intraparietal sulcus in functional systems. However, results were limited in the functional characterization of thalamic nuclei and activity differences in Rich Club and peripheral regions between patients and healthy controls. Limitations of the meta-analytical approach may explain these findings. The systems-level decoding represents a promising approach for formulating hypotheses about brain structure-function relationships within the functional network architecture.