Modelling divisive inhibition in the primary visual cortex from optogenetic circuit mapping data

Recurrent networks are abundant in the neocortex and are recognised as a means of amplifying feedforward thalamic sensory inputs. However, when operating at high gain, which is necessary for this signal amplification, the standard recurrent network firing rate model suffers from increased reaction times to rapidly changing stimuli. Divisive inhibition has been proposed as a means of bypassing this coupling of system gain and time constant. In my thesis I focus on the importance of inhibition in recurrent networks in visual information processing. This was motivated by a recent study where the presence and absence of translaminar inhibition distinguished cells in the primary visual cortex. I apply several divisive inhibition schemes to an existing recurrent network model of simple and complex cells. The schemes are studied analytically and also simulated to assess how well they can be integrated into this existing model whilst simultaneously solving the coupled system gain and time constant problem. Though each scheme has its benefits, I propose that a mixture of schemes is likely in real physiology.This thesis is not currently available via ORA

Electron correlations and dielectric screening in a layered electron gas

SIGLEITItal

Exchange and correlation effects in the Visscher-Falicov model for metal intercalated graphite

SIGLEITItal

Moment sum rules for a layered electron gas

SIGLEITItal

GABAergic interneurons form transient layer-specific circuits in early postnatal neocortex

GABAergic interneurons play key roles in cortical circuits, yet little is known about their early connectivity. Here we use glutamate uncaging and a novel optogenetic strategy to track changes in the afferent and efferent synaptic connections of developing neocortical interneuron subtypes. We find that Nkx2-1-derived interneurons possess functional synaptic connections prior to emerging pyramidal cell networks. Subsequent interneuron circuit maturation is both subtype and layer dependent. Glutamatergic input onto fast spiking (FS), but not somatostatin-positive, non-FS interneurons increases over development. Interneurons of both subtype located in layers (L)4 and L5b engage in transient circuits that disappear after the somatosensory critical period. These include a pathway mediated by L5b somatostatin-positive interneurons that specifically targets L4 during the first postnatal week. The innervation patterns of immature cortical interneuron circuits are thus neither static nor progressively strengthened but follow a layer-specific choreography of transient connections that differ from those of the adult brain

Molecular basis of lipoprotein lipase deficiency in two Austrian families with type I hyperlipoproteinemia.

To determine the molecular basis for type I hyperlipoproteinemia in two Austrian families, the lipoprotein lipase (LPL) gene of two patients exhibiting LPL deficiency was analyzed by Southern blotting and by direct genomic sequencing of DNA amplified by polymerase chain reaction (PCR). All exons of the LPL gene except part of the noncoding region of exon 10, all splice donor and acceptor sites, as well as 430 basepairs of the 5'-region including the promotor were sequenced. A homozygous substitution of adenine for guanine in the fifth exon at cDNA position 818 of the LPL gene was found in both patients. Our sequencing strategy largely ruled out a linkage disequilibrium of the identified nucleotide change with another defect potentially causing the clinical phenotype. The base change described abolishes a normally present AvaII restriction site allowing the identification of carriers of the mutant allele by AvaII digestion of PCR fragments of exon 5; three members of the two families were homozygous for this mutation and ten members were heterozygous. The activity of LPL in postheparin plasma was almost completely absent in homozygotes and about half normal in heterozygotes. The loss of activity was related to LPL protein structure. This mutation alters the amino acid sequence at residue 188 from Gly to Glu. The conformational preferences of the protein chain around position 188 were calculated with the use of a knowledge-based computerized method. The most probable conformation is a beta-turn formed by residues 189-192. The mutation seems to destabilize the beta-turn and/or a yet larger domain critical for substrate alignment

Molecular basis of lipoprotein lipase deficiency in two Austrian families with type I hyperlipoproteinemia.

To determine the molecular basis for type I hyperlipoproteinemia in two Austrian families, the lipoprotein lipase (LPL) gene of two patients exhibiting LPL deficiency was analyzed by Southern blotting and by direct genomic sequencing of DNA amplified by polymerase chain reaction (PCR). All exons of the LPL gene except part of the noncoding region of exon 10, all splice donor and acceptor sites, as well as 430 basepairs of the 5'-region including the promotor were sequenced. A homozygous substitution of adenine for guanine in the fifth exon at cDNA position 818 of the LPL gene was found in both patients. Our sequencing strategy largely ruled out a linkage disequilibrium of the identified nucleotide change with another defect potentially causing the clinical phenotype. The base change described abolishes a normally present AvaII restriction site allowing the identification of carriers of the mutant allele by AvaII digestion of PCR fragments of exon 5; three members of the two families were homozygous for this mutation and ten members were heterozygous. The activity of LPL in postheparin plasma was almost completely absent in homozygotes and about half normal in heterozygotes. The loss of activity was related to LPL protein structure. This mutation alters the amino acid sequence at residue 188 from Gly to Glu. The conformational preferences of the protein chain around position 188 were calculated with the use of a knowledge-based computerized method. The most probable conformation is a beta-turn formed by residues 189-192. The mutation seems to destabilize the beta-turn and/or a yet larger domain critical for substrate alignment