C. J. Lobb, C. J. Wilson, and C. A. Paladini, “High Frequency, Short Latency Disinhibition Bursting of Midbrain Dopaminergic Neurons,” J Neurophysiol, Mar. 2011.

During reinforcement and sequence learning, dopaminergic neurons fire bursts of action potentials. Dopaminergic neurons in vivo receive strong background excitatory and inhibitory inputs, suggesting that one mechanism by which bursts may be produced is disinhibition. Unfortunately, these inputs are lost during slice preparation and are not precisely controlled during in vivo experiments. Here we show that dopaminergic neurons can be shifted into a balanced state in which constant synaptic NMDA and GABAA conductances are mimicked either pharmacologically or using the dynamic clamp. From this state, a disinhibition burst can be evoked by removing the background inhibitory conductance. We demonstrate three functional characteristics of network-based disinhibition that promote high frequency, short latency bursting in dopaminergic neurons. First, we found that increasing the total background NMDA and GABAA synaptic conductances increased the intraburst firing frequency and reduced its latency. Second, we found that the disinhibition burst is sensitive to the proportion of background inhibitory input that is removed. In particular, we found that high frequency, short latency bursts were enhanced by increasing the degree of disinhibition. Third, the time course over which inhibition is removed had a large effect on the burst, namely that synchronous removal of weak inhibitory inputs produces bursts of high intraburst frequency and shorter latency. Our results suggest that fast, more precisely timed bursts can be evoked by complete and synchronous disinhibition of dopaminergic neurons in a high conductance state.