Dysfunctional play and dopamine physiology in the Fischer 344 rat

Juvenile Fischer 344 rats are known to be less playful than other inbred strains, although the neurobiological substrate(s) responsible for this phenotype is uncertain. In the present study, Fischer 344 rats were compared to the commonly used outbred Sprague-Dawley strain on several behavioral and physiological parameters in order to ascertain whether the lack of play may be related to compromised activity of brain dopamine (DA) systems. As expected, Fischer 344 rats were far less playful than Sprague-Dawley rats, with Fischer 344 rats less likely to initiate playful contacts with a playful partner and less likely to respond playfully to these contacts. We also found that Fischer 344 rats showed less of a startle response and greater pre-pulse inhibition (PPI), especially at higher prepulse intensities. The increase in PPI seen in the Fischer 344 rat could be due to reduced DA modulation of sensorimotor gating and neurochemical measures were consistent with Fischer 344 rats releasing less DA than Sprague-Dawley rats. Fast scan cyclic voltammetry (FSCV) revealed Fischer 344 rats had less evoked DA release in dorsal and ventral striatal brain slices and high-performance liquid chromatography revealed Fischer 344 rats to have less DA turnover in the striatum and prefrontal cortex. We also found DA-dependent forms of cortical plasticity were deficient in the striatum and prefrontal cortex of the Fischer 344 rat. Taken together, these data indicate that deficits in play and enhanced PPI of Fischer 344 rats may be due to reduced DA modulation of corticostriatal and mesolimbic/mesocortical circuits critical to the execution of these behaviors

Mechanisms explaining transitions between tonic and phasic firing in neuronal populations as predicted by a low dimensional firing rate model

Several firing patterns experimentally observed in neural populations have been successfully correlated to animal behavior. Population bursting, hereby regarded as a period of high firing rate followed by a period of quiescence, is typically observed in groups of neurons during behavior. Biophysical membrane-potential models of single cell bursting involve at least three equations. Extending such models to study the collective behavior of neural populations involves thousands of equations and can be very expensive computationally. For this reason, low dimensional population models that capture biophysical aspects of networks are needed. \noindent The present paper uses a firing-rate model to study mechanisms that trigger and stop transitions between tonic and phasic population firing. These mechanisms are captured through a two-dimensional system, which can potentially be extended to include interactions between different areas of the nervous system with a small number of equations. The typical behavior of midbrain dopaminergic neurons in the rodent is used as an example to illustrate and interpret our results. \noindent The model presented here can be used as a building block to study interactions between networks of neurons. This theoretical approach may help contextualize and understand the factors involved in regulating burst firing in populations and how it may modulate distinct aspects of behavior.Comment: 25 pages (including references and appendices); 12 figures uploaded as separate file

Misrepresentation of Neuroscience Data Might Give Rise to Misleading Conclusions in the Media: The Case of Attention Deficit Hyperactivity Disorder

BACKGROUND: There is often a huge gap between neurobiological facts and firm conclusions stated by the media. Data misrepresentation in the conclusions and summaries of neuroscience articles might contribute to this gap. METHODOLOGY/PRINCIPAL FINDINGS: Using the case of attention deficit hyperactivity disorder (ADHD), we identified three types of misrepresentation. The first relies on prominent inconsistencies between results and claimed conclusions and was observed in two scientific reports dealing with ADHD. Only one out of the 61 media articles echoing both scientific reports adequately described the results and, thus questioned the claimed conclusion. The second type of misrepresentation consists in putting a firm conclusion in the summary while raw data that strongly limit the claim are only given in the results section. To quantify this misrepresentation we analyzed the summaries of all articles asserting that polymorphisms of the gene coding for the D4 dopaminergic receptor are associated with ADHD. Only 25 summaries out of 159 also mentioned that this association confers a small risk. This misrepresentation is also observed in most media articles reporting on ADHD and the D4 gene. The third misrepresentation consists in extrapolating basic and pre-clinical findings to new therapeutic prospects in inappropriate ways. Indeed, analysis of all ADHD-related studies in mice showed that 23% of the conclusions were overstated. The frequency of this overstatement was positively related with the impact factor of the journal. CONCLUSION/SIGNIFICANCE: Data misrepresentations are frequent in the scientific literature dealing with ADHD and may contribute to the appearance of misleading conclusions in the media. In synergy with citation distortions and publication biases they influence social representations and bias the scientific evidence in favor of the view that ADHD is primarily caused by biological factors. We discuss the social consequences and the causes of data misrepresentations and suggest a few corrective actions

Atomic layer deposition: Low temperature process well adapted to ULSI and TFT technologies

The high k dielectrics is an important materials to be integrate in future Ultra Large Scale Integration (ULSI) and future TFT technology. Indeed, to keep on the Moore\u27s Law curve, the reduction of silicon oxide (SiO2) thickness still required, but this reduction is hindered by tunneling current leakage limit. Consequently, it is important to replace SiO2 by another materials with high dielectric constant. The use of this material in manufacturing of gate dielectric in Thin-film transistor (TFT) and in Complementary Metal Oxide Semiconductor (CMOS) will increase gate capacitance with maintaining a low leakage current. Titanium dioxide is a good candidate due to its high dielectric constant in its rutile crystalline phase (180).This rutile structure is obtained at low temperature (250°C) by ALD deposition when TiO2 is deposited on ruthenium dioxide (RuO2) layer thanks to the small lattice mismatch between these two materials

Zum Zusammenhang von Geschlechterungleichheiten in Bildung, Beruf und Karriere : ein Ausblick

Ziel der folgenden Ausführungen im abschliessenden Teil dieses Sammelbands zur Entwicklung und Genese von geschlechtsspezifischen Bildungsungleichheiten ist es, den Blick zu öffnen in Richtung Berufsleben. Wie sind die verbesserten Bildungsmöglichkeiten von Frauen zu interpretieren? Ist es in den letzten Jahrzehnten gelungen, eines der grundlegendsten gesellschaftlichen Ungleichheitsverhältnisse zu beseitigen? Oder beginnt sich dieses sogar zu verkehren in eine gesellschaftliche Benachteiligung der Männer? Wir gehen bei unseren Überlegungen von der These aus, dass ein Abbau von Benachteiligungen der Frauen im Bildungssystem für sich genommen noch wenig aussagekräftig ist, wenn wir uns mit der klassischen soziologischen Frage der Persistenz bzw. des Wandels von gesellschaftlichen Ungleichheiten befassen wollen. Erst wenn die ganze Verknüpfung von Bildung und gesellschaftlicher Ungleichheit in den Blick genommen wird und sich dabei zeigt, dass Frauen ihre Bildungsgewinne auch in entsprechende Chancen im Beschäftigungssystem umsetzen können, sind ihre verbesserten Bildungschancen ein Gewinn für die Individuen und ein Fortschritt für die Gesellschaft – und erst dann könnten mögliche Bildungsvorteile von Frauen, wie sie in den vorliegenden Aufsätzen z.T. diagnostiziert werden, gar als neue gesellschaftliche Benachteiligungen von Männern skandalisiert werden

Dewey and the democratic curriculum

This paper uses Dewey’s seminal Democracy and Education (1916) as a key text to investigate the concept of the democratic curriculum. I argue that a democratic curriculum is one where a series of educational innovations or procedures are followed. These are: a removal of the exisiting division between ‘academic’ and ‘vocational’ education; pedagogy in the form of discussion and dialogue; negotiation of curriculum aims and objectives with students and other local stakeholders. The focus of attention will be on the English school curriculum (both primary and secondary), especially concerning the National Curriculum, and the debate over ‘standards’ and testing . A tentative link between the democratic curriculum and increased student motivation and participation is made

A Kinetic Model of Dopamine- and Calcium-Dependent Striatal Synaptic Plasticity

Corticostriatal synapse plasticity of medium spiny neurons is regulated by glutamate input from the cortex and dopamine input from the substantia nigra. While cortical stimulation alone results in long-term depression (LTD), the combination with dopamine switches LTD to long-term potentiation (LTP), which is known as dopamine-dependent plasticity. LTP is also induced by cortical stimulation in magnesium-free solution, which leads to massive calcium influx through NMDA-type receptors and is regarded as calcium-dependent plasticity. Signaling cascades in the corticostriatal spines are currently under investigation. However, because of the existence of multiple excitatory and inhibitory pathways with loops, the mechanisms regulating the two types of plasticity remain poorly understood. A signaling pathway model of spines that express D1-type dopamine receptors was constructed to analyze the dynamic mechanisms of dopamine- and calcium-dependent plasticity. The model incorporated all major signaling molecules, including dopamine- and cyclic AMP-regulated phosphoprotein with a molecular weight of 32 kDa (DARPP32), as well as AMPA receptor trafficking in the post-synaptic membrane. Simulations with dopamine and calcium inputs reproduced dopamine- and calcium-dependent plasticity. Further in silico experiments revealed that the positive feedback loop consisted of protein kinase A (PKA), protein phosphatase 2A (PP2A), and the phosphorylation site at threonine 75 of DARPP-32 (Thr75) served as the major switch for inducing LTD and LTP. Calcium input modulated this loop through the PP2B (phosphatase 2B)-CK1 (casein kinase 1)-Cdk5 (cyclin-dependent kinase 5)-Thr75 pathway and PP2A, whereas calcium and dopamine input activated the loop via PKA activation by cyclic AMP (cAMP). The positive feedback loop displayed robust bi-stable responses following changes in the reaction parameters. Increased basal dopamine levels disrupted this dopamine-dependent plasticity. The present model elucidated the mechanisms involved in bidirectional regulation of corticostriatal synapses and will allow for further exploration into causes and therapies for dysfunctions such as drug addiction

Homeostatic mechanisms in dopamine synthesis and release: a mathematical model

<p>Abstract</p> <p>Background</p> <p>Dopamine is a catecholamine that is used as a neurotransmitter both in the periphery and in the central nervous system. Dysfunction in various dopaminergic systems is known to be associated with various disorders, including schizophrenia, Parkinson's disease, and Tourette's syndrome. Furthermore, microdialysis studies have shown that addictive drugs increase extracellular dopamine and brain imaging has shown a correlation between euphoria and psycho-stimulant-induced increases in extracellular dopamine <abbrgrp><abbr bid="B1">1</abbr></abbrgrp>. These consequences of dopamine dysfunction indicate the importance of maintaining dopamine functionality through homeostatic mechanisms that have been attributed to the delicate balance between synthesis, storage, release, metabolism, and reuptake.</p> <p>Methods</p> <p>We construct a mathematical model of dopamine synthesis, release, and reuptake and use it to study homeostasis in single dopaminergic neuron terminals. We investigate the substrate inhibition of tyrosine hydroxylase by tyrosine, the consequences of the rapid uptake of extracellular dopamine by the dopamine transporters, and the effects of the autoreceoptors on dopaminergic function. The main focus is to understand the regulation and control of synthesis and release and to explicate and interpret experimental findings.</p> <p>Results</p> <p>We show that the substrate inhibition of tyrosine hydroxylase by tyrosine stabilizes cytosolic and vesicular dopamine against changes in tyrosine availability due to meals. We find that the autoreceptors dampen the fluctuations in extracellular dopamine caused by changes in tyrosine hydroxylase expression and changes in the rate of firing. We show that short bursts of action potentials create significant dopamine signals against the background of tonic firing. We explain the observed time courses of extracellular dopamine responses to stimulation in wild type mice and mice that have genetically altered dopamine transporter densities and the observed half-lives of extracellular dopamine under various treatment protocols.</p> <p>Conclusion</p> <p>Dopaminergic systems must respond robustly to important biological signals such as bursts, while at the same time maintaining homeostasis in the face of normal biological fluctuations in inputs, expression levels, and firing rates. This is accomplished through the cooperative effect of many different homeostatic mechanisms including special properties of tyrosine hydroxylase, the dopamine transporters, and the dopamine autoreceptors.</p