Question & Methods: 

In vivo burst firing is a key feature of dopamine (DA) neurons. In different midbrain DA subpopulations, phasic excitations code behaviourally-relevant stimuli, i.e. reward-prediction errors, salience, anticipated information or novelty. To study burst firing and define the underlying ionic mechanisms with single-cell resolution, we combined in vivo juxtacellular recordings with neurobiotin-labelling and immunohistochemical identification of individual DA neurons. In vivo recordings were performed in adult isoflurane-anaesthetised wildtype (WT) and ATP-sensitive potassium (K-ATP) channel knockout (Kir6.2-/-) mice. We also established dopamine cell-selective functional suppression of K-ATP channel activity in vivo using viral-mediated expression of dominant-negative Kir6.2 subunits.

Results: 

We found that K-ATP channels selectively control in vivo burst firing in a subpopulation of DA neurons in the medial substantia nigra (m-SN). The percentage of spikes in bursts was three-fold reduced in Kir6.2-/- compared to WT mice. Classification of firing patterns based on visual inspection of autocorrelation-histograms and our newly developed spike-train-model confirmed the shift to predominantly regular single-spike firing in Kir6.2-/- mice. However, similar changes in burst firing were not observed in DA cells located in the lateral SN or the ventral tegmental area. Virus-mediated selective silencing of K-ATP channels demonstrated that the activity of postsynaptic K-ATP channels is sufficient to support bursting in medial SN DA subtypes. Furthermore, viral K-ATP-silencing in m-SN DA neurons induced a novelty-exploration deficit similar to that observed in Kir6.2-/- mice.

Conclusion: 

In summary, K-ATP channels are crucial and selective regulators of in vivo bursting in medial SN DA cells projecting to the dorsomedial striatum and control behavioural responses to novelty.