Cortico-Striatal Spike-Timing Dependent Plasticity After Activation of Subcortical Pathways

Cortico-striatal spike-timing dependent plasticity (STDP) is modulated by dopamine in vitro. The present study investigated STDP in vivo using alternative procedures for modulating dopaminergic inputs. Postsynaptic potentials (PSP) were evoked in intracellularly recorded spiny neurons by electrical stimulation of the contralateral motor cortex. PSPs often consisted of up to three distinct components, likely representing distinct cortico-striatal pathways. After baseline recording, bicuculline (BIC) was ejected into the superior colliculus (SC) to disinhibit visual pathways to the dopamine cells and striatum. Repetitive cortical stimulation (∼60; 0.2 Hz) was then paired with postsynaptic spike discharge induced by an intracellular current pulse, with each pairing followed 250 ms later by a light flash to the contralateral eye (n = 13). Changes in PSPs, measured as the maximal slope normalized to 5-min pre, ranged from potentiation (∼120%) to depression (∼80%). The determining factor was the relative timing between PSP components and spike: PSP components coinciding or closely following the spike tended towards potentiation, whereas PSP components preceding the spike were depressed. Importantly, STDP was only seen in experiments with successful BIC-mediated disinhibition (n = 10). Cortico-striatal high-frequency stimulation (50 pulses at 100 Hz) followed 100 ms later by a light flash did not induce more robust synaptic plasticity (n = 9). However, an elevated post-light spike rate correlated with depression across plasticity protocols (R2 = 0.55, p = 0.009, n = 11 active neurons). These results confirm that the direction of cortico-striatal plasticity is determined by the timing of pre- and postsynaptic activity and that synaptic modification is dependent on the activation of additional subcortical inputs

Challenging the Postwar Narrative: The Art and Agenda of Boris Lurie

Art history is shaped, studied, and taught based on narratives, artistic movements, and the biographies of celebrated artists. While contributing to an understanding of prevalent traditions and artists working in those traditions, these narratives are also constructions of inclusion and exclusion that establish art historical placement for certain artists while relegating others to historical obscurity. It is clear what happens to the critical fortunes of artists who are placed within these narratives. Yet what happens to the artists who do not fit within any of the categories established by these constructions? Are they then to be understood as simply minor artists or perhaps even “outsider artists?” Using the example of Boris Lurie and his critical fortune within the context of the standard art historical narrative of American art of the post World War Two period, this thesis argues for an expanded vision of modern and contemporary art that would accommodate lesser-known artists and offer a nuanced understanding of what American art has been after 1945

Trans-cellular control of synapse properties by a cell type-specific splicing regulator

The recognition of synaptic partners and specification of synaptic properties are fundamental for the function of neuronal circuits. ‘Terminal selector’ transcription factors coordinate the expression of terminal gene batteries that specify cell type-specific properties. Moreover, pan-neuronal alternative splicing regulators have been implicated in directing neuronal differentiation. However, the cellular logic of how splicing regulators instruct specific synaptic properties remains poorly understood. Here, we combine genome-wide mapping of mRNA targets and cell type-specific loss-of-function studies to uncover the contribution of the nuclear RNA binding protein SLM2 to hippocampal synapse specification. Focusing on hippocampal pyramidal cells and SST-positive GABAergic interneurons, we find that SLM2 preferentially binds and regulates alternative splicing of transcripts encoding synaptic proteins, thereby generating cell type-specific isoforms. In the absence of SLM2, cell type-specification, differentiation, and viability are unaltered and neuronal populations exhibit normal intrinsic properties. By contrast, cell type-specific loss of SLM2 results in highly selective, non-cell autonomous synaptic phenotypes, altered synaptic transmission, and associated defects in a hippocampus-dependent memory task. Thus, alternative splicing provides a critical layer of gene regulation that instructs specification of neuronal connectivity in a trans-synaptic manner

Systematic event generator tuning for the LHC

In this article we describe Professor, a new program for tuning model parameters of Monte Carlo event generators to experimental data by parameterising the per-bin generator response to parameter variations and numerically optimising the parameterised behaviour. Simulated experimental analysis data is obtained using the Rivet analysis toolkit. This paper presents the Professor procedure and implementation, illustrated with the application of the method to tunes of the Pythia 6 event generator to data from the LEP/SLD and Tevatron experiments. These tunes are substantial improvements on existing standard choices, and are recommended as base tunes for LHC experiments, to be themselves systematically improved upon when early LHC data is available.Comment: 28 pages. Submitted to European Physical Journal C. Program sources and extra information are available from http://projects.hepforge.org/professor

A cell-type-specific alternative splicing regulator shapes synapse properties in a trans-synaptic manner

The specification of synaptic properties is fundamental for the function of neuronal circuits. "Terminal selector" transcription factors coordinate terminal gene batteries that specify cell-type-specific properties. Moreover, pan-neuronal splicing regulators have been implicated in directing neuronal differentiation. However, the cellular logic of how splicing regulators instruct specific synaptic properties remains poorly understood. Here, we combine genome-wide mapping of mRNA targets and cell-type-specific loss-of-function studies to uncover the contribution of the RNA-binding protein SLM2 to hippocampal synapse specification. Focusing on pyramidal cells and somatostatin (SST)-positive GABAergic interneurons, we find that SLM2 preferentially binds and regulates alternative splicing of transcripts encoding synaptic proteins. In the absence of SLM2, neuronal populations exhibit normal intrinsic properties, but there are non-cell-autonomous synaptic phenotypes and associated defects in a hippocampus-dependent memory task. Thus, alternative splicing provides a critical layer of gene regulation that instructs specification of neuronal connectivity in a trans-synaptic manner

Young European citizens : An individual by context perspective on adolescent European citizenship

This study examined the effects of individual, school-level and country-level variables and their interactions on two components of adolescents’ active European citizenship: trust in European institutions and participation at the European level. For comparison, country-related institutional trust and participation were also predicted. Using multilevel regression models, we re-analysed a subsample of survey data from the International Civic and Citizenship Education Study, collected from 14-year-old students (n = 72,466) in 22 European countries in 2009. Results showed that higher cognitive engagement with politics (e.g., political interest), more opportunities for learning about Europe at school, and country wealth and social equality were positively associated with both aspects of adolescents’ active European citizenship. In contrast to country-related participation, the participatory dimension of active European citizenship was also positively related to a higher socioeconomic status of adolescent’s classroom and family, an association that was more pronounced in less wealthy and post-communist countries

The diagnosis of inherited metabolic diseases by microarray gene expression profiling

<p>Abstract</p> <p>Background</p> <p>Inherited metabolic diseases (IMDs) comprise a diverse group of generally progressive genetic metabolic disorders of variable clinical presentations and severity. We have undertaken a study using microarray gene expression profiling of cultured fibroblasts to investigate 68 patients with a broad range of suspected metabolic disorders, including defects of lysosomal, mitochondrial, peroxisomal, fatty acid, carbohydrate, amino acid, molybdenum cofactor, and purine and pyrimidine metabolism. We aimed to define gene expression signatures characteristic of defective metabolic pathways.</p> <p>Methods</p> <p>Total mRNA extracted from cultured fibroblast cell lines was hybridized to Affymetrix U133 Plus 2.0 arrays. Expression data was analyzed for the presence of a gene expression signature characteristic of an inherited metabolic disorder and for genes expressing significantly decreased levels of mRNA.</p> <p>Results</p> <p>No characteristic signatures were found. However, in 16% of cases, disease-associated nonsense and frameshift mutations generating premature termination codons resulted in significantly decreased mRNA expression of the defective gene. The microarray assay detected these changes with high sensitivity and specificity.</p> <p>Conclusion</p> <p>In patients with a suspected familial metabolic disorder where initial screening tests have proven uninformative, microarray gene expression profiling may contribute significantly to the identification of the genetic defect, shortcutting the diagnostic cascade.</p