The Ferrier Lecture 1998 The molecular biology of consciousness investigated with genetically modified mice

Changeux, Jean‐Pierre

doi:10.1098/rstb.2006.1832

Cited by 29 publications

(25 citation statements)

References 184 publications

(314 reference statements)

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“…In rodents, the anatomical and functional evidence is still scarce but suggests that the frontal fields also have a connectome rich in long-range corticocortical connections (39)(40)(41)(42)(43). In the present work, the PrL/IL field stands out with the highest density of spines.…”

Section: Consequences Of the Deletion Of Nachr β2-subunit On Dendriticmentioning

confidence: 57%

Alterations of cortical pyramidal neurons in mice lacking high-affinity nicotinic receptors

Ballesteros-Yáñez

Benavides-Piccione²,

Bourgeois³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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The neuronal nicotinic acetylcholine receptors (nAChRs) are allosteric membrane proteins involved in multiple cognitive processes, including attention, learning, and memory. The most abundant form of heterooligomeric nAChRs in the brain contains the β2-and α4-subunits and binds nicotinic agonists with high affinity. In the present study, we investigated in the mouse the consequences of the deletion of one of the nAChR components: the β2-subunit (β2 −/− ) on the microanatomy of cortical pyramidal cells. Using an intracellular injection method, complete basal dendritic arbors of 650 layer III pyramidal neurons were sampled from seven cortical fields, including primary sensory, motor, and associational areas, in both β2 −/− and WT animals. We observed that the pyramidal cell phenotype shows significant quantitative differences among different cortical areas in mutant and WT mice. In WT mice, the density of dendritic spines was rather similar in all cortical fields, except in the prelimbic/infralimbic cortex, where it was significantly higher. In the absence of the β2-subunit, the most significant reduction in the density of spines took place in this high-order associational field. Our data suggest that the β2-subunit is involved in the dendritic morphogenesis of pyramidal neurons and, in particular, in the circuits that contribute to the high-order functional connectivity of the cerebral cortex.cerebral cortex | dendrites | dendritic spines | long-range connections | global neuronal workspace N icotinic acetylcholine receptors (nAChRs) are members of the ligand-gated ion channel superfamily of neurotransmitter receptors. They are transmembrane pentamers made up of a single or multiple subunits from the 17 known nAChR subunit genes of the vertebrate genome (9α and 4β). In mammalian neurons, the combinatorial assembly of these subunits generates a broad diversity of receptors with various physiological and pharmacological properties (1). The most abundant form of nAChR heterooligomer in the brain contains the β2-and α4-subunits (2, 3). Moreover, pharmacological experiments and ligand-binding studies demonstrate that nAChRs containing the β2-subunit (β2*nAChRs) bind the neurotransmitter acetylcholine and the drug nicotine with high affinity (4).Strong evidence from diverse sources indicates that nAChRs are involved in cognitive functions in humans and in animal models, including attention and performance in working and associative memory (5). Moreover, alterations of levels of β2*nAChRs are frequently associated with disorders such as schizophrenia, Alzheimer's disease, and autism (6-8). The generation of transgenic mice lacking the β2-subunit (β2) provided a unique opportunity to study the effect of the chronic absence of this receptor on behavior and brain function (9). β2 −/− mice indeed show abnormal passive avoidance, impaired nicotine self-administration, and drug discrimination; they also exhibit a reduced nociceptive response to nicotine, decreased visual acuity, reduced locomotion in a familiar environment, a...

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Section: Consequences Of the Deletion Of Nachr β2-subunit On Dendriticmentioning

confidence: 57%

Alterations of cortical pyramidal neurons in mice lacking high-affinity nicotinic receptors

Ballesteros-Yáñez

Benavides-Piccione²,

Bourgeois³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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“…Indeed, blocking the activation of the cholinergic system in rodent pups blunts the arousal response to hypoxia and increases mortality (7). Mice missing the ␤2-containing nicotinic acetylcholine receptors lack the ability to arouse to the same extent as wild-type mice, and a similar phenotype is observed in newborn pups after chronic exposure of the pregnant mother to nicotine (61).…”

Section: The First Access To Consciousnessmentioning

confidence: 73%

“…The connections with the GNW circuits are not yet fully established. Our view is that it has reached only a lower level of minimal consciousness analogous (though, of course, not identical) to that of a rat/mouse (7,9). A pending question is the status of the preterm fetus born before 26 wk (Ͻ700 g) who has closed eyes and seems constantly asleep.…”

Section: Resultsmentioning

confidence: 99%

“…We deliberately restrict our discussion to a "global neuronal workspace" (GNW) model (5), or metaphorically "a theater of mind" according to Baars (6). In the GNW, multimodal perceptions, emotions and feelings (present), evoked memories (past), together with anticipations of actions (future) become subjectively integrated in a continuously changing and dynamic "flow of consciousness" (7)(8)(9). This then leads to the distinction between the states of consciousness (wakefulness, sleep, coma, general anesthesia) and the content of the conscious experience.…”

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The Emergence of Human Consciousness: From Fetal to Neonatal Life

2009

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A simple definition of consciousness is sensory awareness of the body, the self, and the world. The fetus may be aware of the body, for example by perceiving pain. It reacts to touch, smell, and sound, and shows facial expressions responding to external stimuli. However, these reactions are probably preprogrammed and have a subcortical nonconscious origin. Furthermore, the fetus is almost continuously asleep and unconscious partially due to endogenous sedation. Conversely, the newborn infant can be awake, exhibit sensory awareness, and process memorized mental representations. It is also able to differentiate between self and nonself touch, express emotions, and show signs of shared feelings. Yet, it is unreflective, present oriented, and makes little reference to concept of him/herself. Newborn infants display features characteristic of what may be referred to as basic consciousness and they still have to undergo considerable maturation to reach the level of adult consciousness. The preterm infant, ex utero, may open its eyes and establish minimal eye contact with its mother. It also shows avoidance reactions to harmful stimuli. However, the thalamocortical connections are not yet fully established, which is why it can only reach a minimal level of consciousness. (Pediatr Res 65: 255-260, 2009)

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“…A final review by Jean-Pierre Changeux (Changeux 2006), and based on his Ferrier lecture, describes work investigating molecular contributions to the elementary building blocks of consciousness using genetically modified mice. This focuses particularly on the role of the nicotinic acetylcholine receptor in the brain and functions such as behavioural flexibility and exploration in both social and non-social contexts.…”

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confidence: 99%

Introduction. The neurobiology of social recognition, attraction and bonding

Kendrick

2006

Phil. Trans. R. Soc. B

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The Ferrier Lecture 1998 The molecular biology of consciousness investigated with genetically modified mice

Cited by 29 publications

References 184 publications

Alterations of cortical pyramidal neurons in mice lacking high-affinity nicotinic receptors

Alterations of cortical pyramidal neurons in mice lacking high-affinity nicotinic receptors

The Emergence of Human Consciousness: From Fetal to Neonatal Life

Introduction. The neurobiology of social recognition, attraction and bonding

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