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G Tononi

Publications and source records attributed to G Tononi.

At least 55 records · Page 3Linked to original sources
PubMed1995

Changes in gene expression during the sleep-waking cycle: a new view of activating systems.

Moruzzi pioneered the notion of ascending activating systems that were responsible for the electrophysiological activation characterizing the transition from sleep to waking. This paper proposes to extend the notion of electrophysiological activation to the domain of gene expression. Evidence is reviewed indicating that in the transition between sleep and waking there is, together with a change in neuronal firing patterns, a change in patterns of gene expression in widespread regions of the brain. The hypothesis is presented that changes in the activity of neuromodulatory systems with diffuse projections may subserve the diffuse, tonic and phasic activation of both neuronal responses and of gene expression. Finally, the paper discusses the possibility that such changes in gene expression may be of importance for plastic phenomena and for the functional consequences of sleep.

Animals↗
PubMed1994

A measure for brain complexity: relating functional segregation and integration in the nervous system.

In brains of higher vertebrates, the functional segregation of local areas that differ in their anatomy and physiology contrasts sharply with their global integration during perception and behavior. In this paper, we introduce a measure, called neural complexity (CN), that captures the interplay between these two fundamental aspects of brain organization. We express functional segregation within a neural system in terms of the relative statistical independence of small subsets of the system and functional integration in terms of significant deviations from independence of large subsets. CN is then obtained from estimates of the average deviation from statistical independence for subsets of increasing size. CN is shown to be high when functional segregation coexists with integration and to be low when the components of a system are either completely independent (segregated) or completely dependent (integrated). We apply this complexity measure in computer simulations of cortical areas to examine how some basic principles of neuroanatomical organization constrain brain dynamics. We show that the connectivity patterns of the cerebral cortex, such as a high density of connections, strong local connectivity organizing cells into neuronal groups, patchiness in the connectivity among neuronal groups, and prevalent reciprocal connections, are associated with high values of CN. The approach outlined here may prove useful in analyzing complexity in other biological domains such as gene regulation and embryogenesis.

Animals↗
PubMed1994

Value-dependent selection in the brain: simulation in a synthetic neural model.

Many forms of learning depend on the ability of an organism to sense and react to the adaptive value of its behavior. Such value, if reflected in the activity of specific neural structures (neural value systems), can selectively increase the probability of adaptive behaviors by modulating synaptic changes in the circuits relevant to those behaviors. Neuromodulatory systems in the brain are well suited to carry out this process since they respond to evolutionarily important cues (innate value), broadcast their responses to widely distributed areas of the brain through diffuse projections, and release substances that can modulate changes in synaptic strength. The main aim of this paper is to show that, if value-dependent modulation is extended to the inputs of neural value systems themselves, initially neutral cues can acquire value. This process has important implications for the acquisition of behavioral sequences. We have used a synthetic neural model to illustrate value-dependent acquisition of a simple foveation response to a visual stimulus. We then examine the improvement that ensues when the connections to the value system are themselves plastic and thus become able to mediate acquired value. Using a second-order conditioning paradigm, we demonstrate that auditory discrimination can occur in the model in the absence of direct positive reinforcement and even in the presence of slight negative reinforcement. The discriminative responses are accompanied by value-dependent plasticity of receptive fields, as reflected in the selective augmentation of unit responses to valuable sensory cues. We then consider the time-course during learning of the responses of the value system and the transfer of these responses from one sensory modality to another. Finally, we discuss the relation of value-dependent learning to models of reinforcement learning. The results obtained from these simulations can be directly related to various reported experimental findings and provide additional support for the application of selectional principles to the analysis of brain and behavior.

Animals↗
PubMed1994

The locus coeruleus and immediate-early genes in spontaneous and forced wakefulness.

In this study, we mapped the expression of two immediate-early genes to examine the functional activation of the locus coeruleus and other regions of the rat brain after periods of spontaneous wakefulness or sleep and after sleep deprivation. c-fos and NGFI-A are two immediate-early genes that are rapidly induced by physiological stimuli and can be used as molecular markers of neural activation. We used immunocytochemical detection of Fos and NGFI-A proteins associated with double labeling for tyrosine hydroxylase to identify activated noradrenergic cells. We found that the expression of Fos and NGFI-A was markedly increased in the locus coeruleus and other brain areas both after spontaneous wakefulness and after short periods (3-24 h) of sleep deprivation. Several Fos-positive cells and most NGFI-A positive cells found in the locus coeruleus after periods of spontaneous wakefulness were shown to be noradrenergic. This study demonstrates that wakefulness per se, whether spontaneous or induced by total sleep deprivation, results in the functional activation of identified noradrenergic locus coeruleus cells.

Animals↗
PubMed1994

Immediate-early genes in spontaneous wakefulness and sleep: expression of c-fos and NGFI-A mRNA and protein.

We have recently shown that the expression of two immediate-early genes, c-fos and NGFI-A, is strongly affected by sleep deprivation, In this work, we investigated c-fos and NGFI-A expression after periods of spontaneous wakefulness or sleep. We used in situ hybridization and immunocytochemistry to detect the corresponding mRNA and protein levels, respectively. A first group of rats (S-L) was sacrificed during the light hours at the end of a long period of sleep. A second group (W-L) was sacrificed under similar conditions, except that during the last half hour the animals had been spontaneously awake. A third group (W-D) was sacrificed during the dark hours after a long period of continuous wakefulness. We found that c-fos and NGFI-A expression in several brain areas was increased in W-L and W-D rats with respect to S-L rats. Some of these areas, including the cerebral cortex, basal ganglia, and colliculi, may have been activated by the increased sensory and motor activity associated with waking. The activation of other areas, such as the medial preoptic area of the hypothalamus and some brainstem nuclei, may be more directly related to sleep regulation. These results indicate that many regions showing an increased expression of immediate early genes after wakefulness induced by sleep deprivation are also activated by periods of spontaneous wakefulness.

Journal Article↗
PubMed1992

Synthetic neural modeling applied to a real-world artifact.

We describe the general design, operating principles, and performance of a neurally organized, multiply adaptive device (NOMAD) under control of a nervous system simulated in a computer. The complete system, Darwin IV, is the latest in a series of models based on the theory of neuronal group selection, which postulates that adaptive behavior is the result of selection in somatic time among synaptic populations. The simulated brain of Darwin IV includes visual and motor areas that are connected with NOMAD by telemetry. Under suitable conditions, Darwin IV can be trained to track a light moving in a random path. After such training, it can approach colored blocks and collect them to a home position. Following a series of contacts with such blocks, value signals received through a "snout" that senses conductivity allow it to sort these blocks on the basis of differences in color associated with differences in their conductivity. Darwin IV represents a new approach to synthetic neural modeling (SNM), a technique in which large-scale computer simulations are employed to analyze the interactions among the nervous system, the phenotype, and the environment of a designed organism as behavior develops. Darwin IV retains the advantages of SNM while avoiding the difficulties and pitfalls of attempting to simulate a rich environment in addition to a brain.

Behavior↗
PubMed1992

Modulation of desynchronized sleep through microinjection of alpha 1-adrenergic agonists and antagonists in the dorsal pontine tegmentum of the cat.

Noradrenaline is involved in the regulation of the sleep/waking cycle by acting through various receptor types. In previous studies we investigated the role of beta- and alpha 2-adrenergic receptors through local microinjections of various drugs into the dorsal pontine tegmentum (DPT) of the cat. This region is known to be crucially involved in desynchronized sleep execution. In this study we examined the role of alpha 1-adrenergic receptors. The alpha 1-agonist methoxamine and the alpha 1-antagonist prazosin were injected into the DPT of freely moving, unanaesthetized cats. We found that methoxamine notably reduced desynchronized sleep, and that this effect was both dose-dependent and site-specific. These effects were prevented by the subsequent injection of prazosin. On the other hand, the injection into the DPT of prazosin alone produced scarce or inconsistent effects on the sleep/waking cycle.

Animals↗
PubMed1992

Effects of sleep deprivation on fos-like immunoreactivity in the rat brain.

The molecular mechanisms involved in sleep regulation and function are largely unknown, and our understanding of the localization of such mechanisms within specific brain structures is still incomplete. In this work, we explored the consequences of sleep deprivation by the immunocytochemical mapping of the induction of the protein product of the immediate early gene c-fos in the brain of sleep-deprived rats. The expression of Fos protein is an indicator of neuronal activity. In addition, since immediate early genes can function as "third messengers" and regulate the transcription of a number of target genes, their induction could be directly relevant to the homeostasis and functions of sleep. The present results show that, as a result of 24 hours of manual sleep deprivation, Fos-like immunoreactive cells are found in specific brain areas. These areas include the medial preoptic area of the hypothalamus, the nucleus accumbens, the lateral septum, several regions of the dorsal pontine tegmentum (central gray, dorsal raphe, locus coeruleus, pedunculopontine and laterodorsal tegmental nuclei, parabrachial nuclei) and an area medial to the parabigeminal nucleus at the ponto-mesencephalic junction. Some of these areas had already been implicated in slow-wave sleep and desynchronized sleep regulation.

Animals↗
PubMed1991

Modeling perceptual grouping and figure-ground segregation by means of active reentrant connections.

The segmentation of visual scenes is a fundamental process of early vision, but the underlying neural mechanisms are still largely unknown. Theoretical considerations as well as neurophysiological findings point to the importance in such processes of temporal correlations in neuronal activity. In a previous model, we showed that reentrant signaling among rhythmically active neuronal groups can correlate responses along spatially extended contours. We now have modified and extended this model to address the problems of perceptual grouping and figure-ground segregation in vision. A novel feature is that the efficacy of the connections is allowed to change on a fast time scale. This results in active reentrant connections that amplify the correlations among neuronal groups. The responses of the model are able to link the elements corresponding to a coherent figure and to segregate them from the background or from another figure in a way that is consistent with the so-called Gestalt laws.

Animals↗
PubMed1991

Suppression of desynchronized sleep through microinjection of the alpha 2-adrenergic agonist clonidine in the dorsal pontine tegmentum of the cat.

The relationships between sleep-waking states and the activity of the noradrenergic system are controversial. In particular, according to an influential model of desynchronized sleep (DS) generation, the arrest of firing of noradrenergic neurons in the locus coeruleus should enhance DS, due to the release from inhibition of executive neurons located in the nearby pontine tegmentum. Since locus coeruleus neurons are strongly inhibited by alpha 2-adrenergic agonists like clonidine, this agent would be expected to increase DS. Yet clonidine powerfully decreases DS when injected systemically in several species. In this study, clonidine was microinjected locally into the dorsal pontine tegmentum of the cat, a region which comprises anatomically the whole locus coeruleus complex and which plays a key role in the generation of DS. In accord with the results of systemic experiments, bilateral injections of clonidine almost suppressed DS and unilateral injections consistently reduced it. The effects were dose dependent and site specific. It is suggested that clonidine may suppress DS by acting additionally on non-noradrenergic cell groups located in the dorsal pontine tegmentum.

Adrenergic alpha-Agonists↗
PubMed1991

Effects of local pontine injection of noradrenergic agents on desynchronized sleep of the cat.

Brain noradrenergic (NA) systems have often been implicated in the regulation of desynchronized sleep (DS). The present experiments investigate the effects on DS of the microinjection, into the cat dorsal pontine tegmentum (DPT), of the alpha 2-agonist clonidine (CLON), the beta-agonist isoproterenol and the beta-antagonist propranolol. The DPT comprises most NA neurons belonging to the locus coeruleus (LC) complex, as well as other cell groups thought to be crucially involved in DS generation. Cats were implanted with standard electrodes (electroencephalogram, electrooculogram and electromyogram, PGO waves, hippocampal activity) and with guide tubes aimed at the DPT. Unilateral or bilateral injections (0.25 microliter) were performed by way of thin cannulae inserted through the guide tubes. Polygraphic activity was then recorded in daily sessions lasting 4 h and scored according to standard criteria. Bilateral injections of CLON into the DPT greatly reduced DS, while unilateral injections were much less effective. Since CLON is known to powerfully inhibit NA LC neurons, its effect was thus opposite to that expected on the basis of the reciprocal interaction model of DS generation, which postulates that NA neurons in the LC inhibit DS-executive cells located in the pontine reticular formation. Bilateral injections of the beta-agonist isoproterenol also reduced DS, while the beta-antagonist propranolol consistently enhanced it, the latter largely due to an increased number of DS episodes. These effects were dose-dependent and strictly site-specific, since injections in immediately neighboring structures were ineffective.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Changes in pontine muscarinic receptor binding during sleep-waking states in the rat.

Number and affinity of pontine muscarinic receptors were examined in rats sacrificed during polygraphically defined wakefulness (W), synchronized sleep (S) and desynchronized sleep (D). Saturation binding assays with (-)-[3H]quinuclidinyl benzilate [( 3H]QNB) showed that muscarinic receptor levels were higher in W and D than in S. These findings indicate that brain receptor levels may change in relation to sleep-waking states. The significance of such changes in relation to the time course of sleep-waking states, as well as the possibility that the number of pontine muscarinic receptors plays a role in the triggering of D are discussed.

Animals↗
PubMed1990

Noradrenergic receptor binding during sleep-waking states in the rat.

It was recently shown that the number of muscarinic receptors in the rat pons undergoes short-term changes which are related to sleep-waking states and may thus play a role in determining their time course. In this study we investigated whether also noradrenergic receptors change in relation to polygraphically documented wakefulness (W), synchronized (S) and desynchronized sleep (D). Brain noradrenergic systems are deeply involved in the control of vigilance states, and a new hypothesis about the function of D has suggested that adrenoceptors would be desensitized or downregulated during W and upregulated during D. We examined the number of alpha 1-, alpha 2- and beta-adrenergic receptors in the forebrain and the cerebellum, and the number and affinity of alpha 2-receptors in a brainstem region including the locus coeruleus. The results indicate that the number of alpha 1-, alpha 2- and beta-adrenergic receptors does not change in relation to sleep-waking states either in the forebrain or in the cerebellum, and that the number and the affinity of alpha 2-adrenergic receptors in the brainstem are stable as well.

Animals↗
PubMed1989

Modulation of desynchronized sleep through microinjection of beta-adrenergic agonists and antagonists in the dorsal pontine tegmentum of the cat.

Brain noradrenergic systems have often been implicated in the regulation of desynchronized sleep (DS). In particular, the reciprocal interaction model of DS generation postulates that noradrenergic neurons in the locus coeruleus inhibit DS-executive cells located in the pontine reticular formation. Accordingly, since noradrenergic inhibition is generally mediated by beta-receptors, one should expect beta-agonists to decrease and beta-antagonists to increase DS. However, systemic injection experiments yielded just the opposite results. Assuming that local microinjection techniques were better suited to testing the model, beta-agonists and antagonists were directly infused into the dorsal pontine tegmentum (DPT), a region crucially implicated in the generation of DS. Cats were implanted with standard electrodes for polygraphic recordings and with guide tubes for chemical microinjections. It was observed that, when injected into the DPT, the beta-agonist isoproterenol almost suppressed DS, while the beta-antagonist propranolol consistently enhanced it, the latter largely due to an increased number of DS episodes. These effects were dose-dependent and strictly site-specific, since injections in immediately neighbouring structures were ineffective. These results: (a) confirm that cell groups located in the DPT play a key role in the generation of DS, and (b) indicate that they undergo a strong noradrenergic modulation, being inhibited by beta-receptor stimulation and disinhibited by beta-receptor blockade as predicted by the reciprocal interaction model.

Adrenergic beta-Agonists↗
PubMed1989

Inhibition of vestibulospinal reflexes during the episodes of postural atonia induced by unilateral lesion of the locus coeruleus in the decerebrate cat.

1. The spontaneous EMG activity of the forelimb extensor triceps brachii of both sides as well as their responses to roll tilt of the animal at 0.15 Hz, +/- 10 degrees leading to sinusoidal stimulation of labyrinth receptors were tested in precollicular decerebrate cats, before and after unilateral electrolytic lesion of the locus coeruleus (LC). 2. Lesion of the LC of one side decreased the tonic contraction of the ipsilateral limb extensors, but greatly increased the amplitude of modulation and the response gain of the corresponding triceps brachii to animal tilt; however, no change in the phase angle of the responses was observed. A slight increase in the response gain affected also the contralateral triceps brachii. 3. The postural asymmetry described above was followed from time to time by short-lasting episodes of postural atonia, which affected not only the ipsilateral but also the contralateral limb extensors. These episodes were also associated with a suppression of the EMG responses of the triceps brachii of both sides to sinusoidal stimulation of labyrinth receptors. 4. The episodes of postural atonia which appeared after unilateral lesion of the LC were not associated with rapid eye movements; however, the slow horizontal eye movements, which may occur in normal decerebrate animals, increased in amplitude throughout these episodes. Both the postural atonia as well as the related suppression of the vestibulospinal reflexes, which lasted for 5-10 min, disappeared either spontaneously or following acoustic or somatosensory stimulations. 5. Histological controls indicated that unilateral lesions limited to the caudal part of the LC produced only a permanent decrease in postural activity of the ipsilateral limbs, associated with an increase in gain of the vestibulospinal reflex. However, in order to elicit episodes of bilateral postural atonia associated with the suppression of the vestibulospinal reflexes it was necessary to extend the lesion to more rostral aspects of the LC. 6. Since the effects described above were similar to those elicited in decerebrate cats by local injection of cholinergic agonists into the dorsal part of the pontine reticular formation, we postulated that the postural atonia as well as the related suppression of the vestibulospinal reflexes was due to transient release from LC inhibition of these dorsal pontine reticular structures, which might in turn excite the medullary reticulospinal neurons, thus leading to inhibition of the extensor motoneurons.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗