Showing papers by "Giulio Tononi published in 2000"

Correlates of Sleep and Waking in Drosophila melanogaster

Abstract: Drosophila exhibits a circadian rest-activity cycle, but it is not known whether fly rest constitutes sleep or is mere inactivity. It is shown here that, like mammalian sleep, rest in Drosophila is characterized by an increased arousal threshold and is homeostatically regulated independently of the circadian clock. As in mammals, rest is abundant in young flies, is reduced in older flies, and is modulated by stimulants and hypnotics. Several molecular markers modulated by sleep and waking in mammals are modulated by rest and activity in Drosophila, including cytochrome oxidase C, the endoplasmic reticulum chaperone protein BiP, and enzymes implicated in the catabolism of monoamines. Flies lacking one such enzyme, arylalkylamine N-acetyltransferase, show increased rest after rest deprivation. These results implicate the catabolism of monoamines in the regulation of sleep and waking in the fly and suggest that Drosophila may serve as a model system for the genetic dissection of sleep.

A Universe of Consciousness: How Matter Becomes Imagination

Abstract: In A Universe of Consciousness, Gerald Edelman builds on the radical ideas he introduced in his monumental trilogy-Neural Darwinism, Topobiology, and The Remembered Present-to present for the first time an empirically supported full-scale theory of consciousness. He and the neurobiolgist Giulio Tononi show how they use ingenious technology to detect the most minute brain currents and to identify the specific brain waves that correlate with particular conscious experiences. The results of this pioneering work challenge the conventional wisdom about consciousness.

Theoretical Neuroanatomy: Relating Anatomical and Functional Connectivity in Graphs and Cortical Connection Matrices

Abstract: Neuroanatomy places critical constraints on the functional connectivity of the cerebral cortex. To analyze these constraints we have examined the relationship between structural features of networks (expressed as graphs) and the patterns of functional connectivity to which they give rise when implemented as dynamical systems. We selected among structurally varying graphs using as selective criteria a number of global information-theoretical measures that characterize functional connectivity. We selected graphs separately for increases in measures of entropy (capturing statistical independence of graph elements), integration (capturing their statistical dependence) and complexity (capturing the interplay between their functional segregation and integration). We found that dynamics with high complexity were supported by graphs whose units were organized into densely linked groups that were sparsely and reciprocally interconnected. Connection matrices based on actual neuroanatomical data describing areas and pathways of the macaque visual cortex and the cat cortex showed structural characteristics that coincided best with those of such complex graphs, revealing the presence of distinct but interconnected anatomical groupings of areas. Moreover, when implemented as dynamical systems, these cortical connection matrices generated functional connectivity with high complexity, characterized by the presence of highly coherent functional clusters. We also found that selection of graphs as they responded to input or produced output led to increases in the complexity of their dynamics. We hypothesize that adaptation to rich sensory environments and motor demands requires complex dynamics and that these dynamics are supported by neuroanatomical motifs that are characteristic of the cerebral cortex.

Differential Expression of Plasticity-Related Genes in Waking and Sleep and Their Regulation by the Noradrenergic System

Abstract: Behavioral studies indicate that the ability to acquire long-term memories is severely impaired during sleep. It is unclear, however, why the highly synchronous discharge of neurons during sleep should not be followed by the induction of enduring plastic changes. Here we show that the expression of phosphorylated CRE-binding protein, Arc, and BDNF, three genes whose induction is often associated with synaptic plasticity, is high during waking and low during sleep. We also show that the induction of these genes during waking depends on the activity of the noradrenergic system, which is high in waking and low in sleep. These molecular results complement behavioral evidence and provide a mechanism for the impairment of long-term memory acquisition during sleep.

On the Functional Significance of c-fos Induction During the Sleep-waking Cycle

Abstract: A striking finding in recent years has been that the transition from sleep to waking is accompanied in many brain regions by a widespread activation of c-fos and other immediate-early genes (IEGs). IEGs are induced by various electrical or chemical signals to which neural cells are exposed and their protein products act as transcription factors to regulate the expression of other genes. After a few hours of sleep, the expression of these transcription factors in the brain is absent or restricted to very few cells. However, after a few hours of spontaneous waking or sleep deprivation, the expression of c-fos and other IEGs is high in cerebral cortex, hypothalamus, septum, and several thalamic and brainstem nuclei. While cells expressing c-fos during waking are widely distributed, they represent only a subset of all neurons in any given area. These observations raise several questions: Why is c-fos expressed during waking and not during sleep? Is waking always accompanied by c-fos induction? Which subset of cells express c-fos during waking and why only a subset? Once c-fos has been induced, what are the functional consequences of its activation? In this review, we summarize our current understanding of the meaning of c-fos activation in the brain in relation to the sleep-waking cycle and suggest that c-fos induction in the cerebral cortex during waking might be related to the occurrence of plastic phenomena.

Vigilance nucleic acids and related diagnostic, screening and therapeutic methods

Abstract: The invention provides methods of identifying compounds that alters vigilance, by contacting an invertebrate with a candidate compound, evaluating a vigilance property in the contacted invertebrate, and determining if the candidate compound alters the vigilance property in the contacted invertebrate. Also provided are isolated vigilance nucleic acid molecules. Methods for diagnosing and treating vigilance disorders, for determining and altering vigilance levels, and for screening for therapeutic compounds useful for treating vigilance disorders and altering vigilance level, are also provided.