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Recent experimental studies and theoretical models have begun to address the challenge of establishing a causal link between subjective conscious experience and measurable neuronal activity. The present review focuses on the well-delimited issue of how an external or internal piece of information goes beyond nonconscious processing and gains access to conscious processing, a transition characterized by the existence of a reportable subjective experience. Converging neuroimaging and neurophysiological data, acquired during minimal experimental contrasts between conscious and nonconscious processing, point to objective neural measures of conscious access: late amplification of relevant sensory activity, long-distance cortico-cortical synchronization at beta and gamma frequencies, and "ignition" of a large-scale prefronto-parietal network. We compare these findings to current theoretical models of conscious processing, including the Global Neuronal Workspace (GNW) model according to which conscious access occurs when incoming information is made globally available to multiple brain systems through a network of neurons with long-range axons densely distributed in prefrontal, parieto-temporal, and cingulate cortices. The clinical implications of these results for general anesthesia, coma, vegetative state, and schizophrenia are discussed.

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Release of the neurotransmitter dopamine in the mesolimbic system of the brain mediates the reinforcing properties of several drugs of abuse, including nicotine. Here we investigate the contribution of the high-affinity neuronal nicotinic acetylcholine receptor to the effects of nicotine on the mesolimbic dopamine system in mice lacking the beta2 subunit of this receptor. We found that nicotine stimulates dopamine release in the ventral striatum of wild-type mice but not in the ventral striatum of beta2-mutant mice. Using patch-clamp recording, we show that mesencephalic dopaminergic neurons from mice without the beta2 subunit no longer respond to nicotine, and that self-administration of nicotine is attenuated in these mutant mice. Our results strongly support the idea that the beta2-containing neuronal nicotinic acetylcholine receptor is involved in mediating the reinforcing properties of nicotine.

Pentameric ligand-gated ion channels from the Cys-loop family mediate fast chemo-electrical transduction, but the mechanisms of ion permeation and gating of these membrane proteins remain elusive. Here we present the X-ray structure at 2.9 A resolution of the bacterial Gloeobacter violaceus pentameric ligand-gated ion channel homologue (GLIC) at pH 4.6 in an apparently open conformation. This cationic channel is known to be permanently activated by protons. The structure is arranged as a funnel-shaped transmembrane pore widely open on the outer side and lined by hydrophobic residues. On the inner side, a 5 A constriction matches with rings of hydrophilic residues that are likely to contribute to the ionic selectivity. Structural comparison with ELIC, a bacterial homologue from Erwinia chrysanthemi solved in a presumed closed conformation, shows a wider pore where the narrow hydrophobic constriction found in ELIC is removed. Comparative analysis of GLIC and ELIC reveals, in concert, a rotation of each extracellular beta-sandwich domain as a rigid body, interface rearrangements, and a reorganization of the transmembrane domain, involving a tilt of the M2 and M3 alpha-helices away from the pore axis. These data are consistent with a model of pore opening based on both quaternary twist and tertiary deformation.

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The subjective experience of perceiving visual stimuli is accompanied by objective neuronal activity patterns such as sustained activity in primary visual area (V1), amplification of perceptual processing, correlation across distant regions, joint parietal, frontal, and cingulate activation, ␥-band oscillations, and P300 waveform. We describe a neuronal network model that aims at explaining how those physiological parameters may cohere with conscious reports. The model proposes that the step of conscious perception, referred to as access awareness, is related to the entry of processed visual stimuli into a global brain state that links distant areas including the prefrontal cortex through reciprocal connections, and thus makes perceptual information reportable by multiple means. We use the model to simulate a classical psychological paradigm: the attentional blink. In addition to reproducing the main objective and subjective features of this paradigm, the model predicts an unique property of nonlinear transition from nonconscious processing to subjective perception. This all-or-none dynamics of conscious perception was verified behaviorally in human subjects.

Despite their lack of language, human infants and several animal species possess some elementary abilities for numerical processing. These include the ability to recognize that a given numerosity is being presented visually or auditorily, and, at a later stage of development, the ability to compare two nume-rosities and to decide which is larger. We propose a model for the development of these abilities in a formal neuronal network. Initially, the model is equipped only with unordered numerosity detectors. It can therefore detect the numerosity of an input set and can be conditioned to react accordingly. In a later stage, the addition of a short-term memory network is shown to be sufficient for number comparison abilities to develop. Our computer simulations account for several phenomena in the numerical domain, including the distance effect and Fechner's law for numbers. They also demonstrate that infants' numerosity detection abilities may be explained without assuming that infants can count. The neurobiological bases of the critical components of the model are discussed.