Tuning of Neuronal Interactions in the Lateral Ventral Tegmental Area by Dopamine Sensitivity

Abstract

The Ventral Tegmental Area (VTA) contains a considerable population of rhythmically firing dopaminergic neurons, which are influenced by auto-inhibition due to extra-synaptic dopamine release resulting in volume transmission. Using a Multi-Electrode-Array we simultaneously recorded in vitro from multiple VTA dopamine neurons in the rat and studied their mutual interactions. We observed that the dopamine sensitivity (EC50) of the neurons (i.e. the relation between dopamine concentration and firing rate) was quite variable within the recorded population. The interactions between pairs of neurons were quantified using the Granger causality. We found that the dopamine sensitivity determined the role of a neuron in the local VTA population. Highly sensitive neurons became followers (of the population rhythm), whereas less sensitive dopamine neurons played a more leading role. This was confirmed by the application of sulpiride which reduces the dopamine sensitivity of all neurons through competition and abolishes the structure in the interactions. These findings imply that therapeutics, which have an easy to understand effect on firing rate, could have a more complicated effect on the functional organization of the local VTA population, through volume transmission principles.