Dopamine signaling as a neural correlate of consciousness.
ABSTRACT The neural correlates of consciousness are largely unknown but many neural circuits are likely to be involved. Our experiments with mice that cannot synthesize dopamine suggest that dopamine signaling is a critical component necessary for the expression of consciousness. Although dopamine-deficient mice are awake and respond to many stimuli, they are unmotivated and have profound deficits in all but the simplest learning tasks. Dopamine-deficient mice are unable to attend to salient sensory information, integrate it with prior experience, store it in long-term memory, or choose appropriate actions. While clearly conscious from a general anesthetic point of view, dopamine-deficient mice have marginal arousal and appear to be virtually unconscious from a behavioral point of view. Restoration of dopamine signaling within the striatum by viral gene therapy strategies restores most behaviors. Therefore, I propose that dopaminergic modulation of glutamatergic inputs from the cortex and thalamus onto medium spiny neurons in the striatum contributes to cognition and the expression of consciousness.
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ABSTRACT: Dopamine (DA) is a key transmitter in the basal ganglia, yet DA transmission does not conform to several aspects of the classic synaptic doctrine. Axonal DA release occurs through vesicular exocytosis and is action potential- and Ca²⁺-dependent. However, in addition to axonal release, DA neurons in midbrain exhibit somatodendritic release by an incompletely understood, but apparently exocytotic, mechanism. Even in striatum, axonal release sites are controversial, with evidence for DA varicosities that lack postsynaptic specialization, and largely extrasynaptic DA receptors and transporters. Moreover, DA release is often assumed to reflect a global response to a population of activities in midbrain DA neurons, whether tonic or phasic, with precise timing and specificity of action governed by other basal ganglia circuits. This view has been reinforced by anatomical evidence showing dense axonal DA arbors throughout striatum, and a lattice network formed by DA axons and glutamatergic input from cortex and thalamus. Nonetheless, localized DA transients are seen in vivo using voltammetric methods with high spatial and temporal resolution. Mechanistic studies using similar methods in vitro have revealed local regulation of DA release by other transmitters and modulators, as well as by proteins known to be disrupted in Parkinson's disease and other movement disorders. Notably, the actions of most other striatal transmitters on DA release also do not conform to the synaptic doctrine, with the absence of direct synaptic contacts for glutamate, GABA, and acetylcholine (ACh) on striatal DA axons. Overall, the findings reviewed here indicate that DA signaling in the basal ganglia is sculpted by cooperation between the timing and pattern of DA input and those of local regulatory factors.Neuroscience 09/2011; 198:112-37. · 3.38 Impact Factor