2002 Special issueThe computational role of dopamine D1 receptors in working memory
Section snippets
The prefrontal cortex and working memory
The prefrontal cortex (PFC) is critically involved in the ability to integrate previously acquired information with recent sensory input to guide action according to a goal state (Fuster, 1997, Goldman-Rakic, 1996). Such processes have been termed working memory and allow forthcoming actions to be planned in a contextually relevant and flexible manner. In animal experiments, working memory is often invoked by introducing a delay between the presentation of a relevant stimulus and a choice
Dopaminergic modulation of prefrontal neurons and working memory
One important source of extrinsic modulation in the PFC is via dopamine. Dopaminergic input to the PFC originates from a small group of mesencephalic neurons (in the ventral tegmentum and substantia nigra) that projects to various cortical areas, flooding them with dopamine in a diffuse manner (Cass and Gerhardt, 1995, Garris et al., 1993, Wightman and Zimmerman, 1990). Dopamine levels in the PFC specifically rise during working memory tasks (Watanabe, Kodama, & Hikosaka, 1997) and dopaminergic
Computational analysis of dopamine action in prefrontal cortex
To assess the impact of dopamine on neural network dynamics, a series of PFC network models with varying levels of abstractness were developed (Durstewitz et al., 1999, Durstewitz et al., 2000a). The basic idea underlying this approach was to start with a model that captured essential electrophysiological characteristics of neural networks probed in behaving monkeys during the performance of working memory tasks and that implemented basic biophysical properties of PFC neurons derived from in
Experimental evidence for the model
Although the behavioral, in vivo and in vitro findings summarized in Section 2 are consistent with the model described here, direct evidence is still lacking. In favor of the model, behavioral findings indicate that animals where the dopaminergic input to the PFC has been lesioned by 6-OHDA are in fact not only more susceptible to distraction (as postulated by the model), they actually show improved performance on tasks requiring high response flexibility (Crofts et al., 2001, Roberts et al.,
Conclusions
Based on the simulation results and the available experimental evidence, the dopamine system might have a somewhat different function than commonly believed. Dopaminergic midbrain neurons typically exhibit a phasic burst in response to a stimulus indicating (or predicting) behaviorally important events or at the onset of a working memory task (Schultz, 1998). Yet it is important to note that although dopamine midbrain neurons respond transiently to a novel or important event, dopamine levels in
Acknowledgements
DD was supported by a research grant (DU 354/2-1) from the Deutsche Forschungsgemeinschaft. The authors would like to thank Dr Terrence Sejnowski for providing the stimulating environment under which many of the ideas presented here were developed, and for his input and discussions. We furthermore thank Dr Kirsten Weibert for helpful comments on the manuscript.
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Both authors contributed equally to the ideas put forward in this paper.