Drumming with dopamine neurons:Resonance and synchronization in the Ventral Tegmental Area

The ventral tegmental area (VTA) is a dopaminergic nucleus in the midbrain with the propensity to exhibit spontaneous intrinsic rhythmic activity in the 1-5 Hz frequency range (ex vivo). Here, we combine in-vitro simultaneous action potential recording from a 60 channel multi-electro-array with experimental manipulations to investigate the local VTA network. First, we increased the neuronal excitability with two compounds (extracellular potassium and glutamate). The functional connectivity between dopamine neurons was measured with the Paired-Phase-Consistency. Manipulating excitability had distinct and specific consequences for functional connectivity in the VTA network separate from the e_ects on neuronal firing rates. Thus the functional connectivity within the VTA is an emergent phenomena. Secondly, we observed that the dopamine sensitivity (EC50) of the neurons (the relation between dopamine concentration and firing rate) was variable within the recorded population. Dopamine sensitivity was found to determine the role of a neuron in the local VTA network. Highly sensitive neurons became followers, whereas less sensitive dopamine neurons played a more leading role (quantified by Granger causality). Dopamine sensitivity thus tunes the network interactions between VTA dopamine neurons. Thirdly, the dopamine neuron population activity was manipulated with precise laser pulse stimulation (optogenetics). The filter characteristics of the VTA dopamine neurons, measured with this technique, allow the VTA to encode timing information in its input important for reward prediction. Our study reveals emergent network phenomena in the VTA relevant for pharmacology targeting dopamine and the function of the local VTA network in relation to reward prediction, memory and learning