Abstract
Dopamine transmission in the prefrontal cortex plays an important role in reward based learning, working memory and attention. Dopamine is thought to be released non-synaptically into the extracellular space and to reach distant receptors through diffusion. This simulation study examines how the dopamine signal might be decoded by the recipient neuron. The simulation was based on parameters from the literature and on our own quantified, structural data from macaque prefrontal area 10. The change in extracellular dopamine concentration was estimated at different distances from release sites and related to the affinity of the dopamine receptors. Due to the sparse and random distribution of release sites, a transient heterogeneous pattern of dopamine concentration emerges. Our simulation predicts, however, that at any point in the simulation volume there is sufficient dopamine to bind and activate high-affinity dopamine receptors. We propose that dopamine is broadcast to its distant receptors and any change from the local baseline concentration might be decoded by a transient change in the binding probability of dopamine receptors. Dopamine could thus provide a graduated ‘teaching’ signal to reinforce concurrently active synapses and cell assemblies. In conditions of highly reduced or highly elevated dopamine levels the simulations predict that relative changes in the dopamine signal can no longer be decoded, which might explain why cognitive deficits are observed in patients with Parkinson’s disease, or induced through drugs blocking dopamine reuptake.
Highlights
The dopamine signal in the prefrontal cortex (PFC) is crucial for working memory as well as for reinforcement learning [1,2,3]
The dopamine concentration at steady state varies between 9.5 nM up to 250 nM (Boxplot Figure 1D), which reveals that at the baseline levels maintained during tonic release, the dopamine receptors in their high affinity state are activated everywhere in the volume
Our results address important questions about how dopamine neurons encode their signal, how this signal is decoded by the recipient neurons in the PFC and by what means cell assemblies and individual synapses are modulated?
Summary
The dopamine signal in the prefrontal cortex (PFC) is crucial for working memory as well as for reinforcement learning [1,2,3]. Models of the dopamine signal in the densely innervated striatum indicate that the timing of dopamine release in relation to glutamatergic synaptic activity can provide the selectivity of dopamine as a reinforcement signal [9,10] Consistent with these predictions, a bidirectional interaction of activated NMDA- and dopamine D1 receptor has been observed experimentally. The activated NMDA receptors in turn increase the number of available D1 receptors on the membrane of spines [11,12,13] This reciprocal interaction has further been proposed to underlie the modulatory effect of dopamine on synaptic plasticity and learning in neuronal networks [14]
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