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

Abstract

The question is raised of the relevance of experimental work with the mouse and some of its genetically modified individuals in the study of consciousness. Even if this species does not go far beyond the level of 'minimal consciousness', it may be a useful animal model to examine the elementary building blocks of consciousness using the methods of molecular biology jointly with investigations at the physiological and behavioural levels. These building blocks which are anticipated to be universally shared by higher organisms (from birds to humans) may include: (i) the access to multiple states of vigilance, like wakefulness, sleep, general anaesthesia, etc.; (ii) the capacity for global integration of several sensory and cognitive functions, together with behavioural flexibility resulting in what is referred to as exploratory behaviour, and possibly a minimal form of intentionality. In addition, the contribution of defined neuronal nicotinic receptors species to some of these processes is demonstrated and the data discussed within the framework of recent neurocomputational models for access to consciousness.

Figure 1

The neuronal workspace hypothesis: schematic of brain networks comprising multiple specialized processors and a central network of high-level areas interconnecting them by neurons with long-range axons (from Dehaene et al. 1998, 2003).

Figure 2

The nicotinic acetylcholine receptor: a typical allosteric membrane protein. Reconstituted atomic model of the α7 receptor (a) and in the resting closed (b(i)) and open-channel (b(ii)) states (from Taly et al. 2005).

Figure 3

Presence of functional nicotinic receptors in prefrontal cortex slices. Opposite effects of nicotine and muscarine on post-synaptic potentials in layers II/III neurons (from Vidal & Changeux 1993).

Figure 4

Nicotinic receptors and states of vigilance: consequences of the deletion of the β2 subunit on microarousals (from Lena et al. 2004) and on the respiratory arousal of newborn mice chronically exposed in utero to nicotine (nicotine exposure destabilizes breathing; from Cohen et al. 2005).

Figure 5

Nicotinic receptors and content of consciousness: consequences of the deletion of the β2 subunit and of its stereotaxic re-expression in the ventral tegmental area on self-administration of nicotine and on the navigatory behaviour of the mouse (from Maskos et al. 2005); VEC, re-expressed β2 subunit.