PT  - JOURNAL ARTICLE
AU  - Rebekah C. Evans
AU  - Manhua Zhu
AU  - Zayd M. Khaliq
TI  - Dopamine inhibition differentially controls excitability of SNc dopamine neuron subpopulations through recruitment of T-type calcium channels
AID  - 10.1523/JNEUROSCI.0117-17.2017
DP  - 2017 Mar 06
TA  - The Journal of Neuroscience
PG  - 0117-17
4099  - http://www.jneurosci.org/content/early/2017/03/06/JNEUROSCI.0117-17.2017.short
4100  - http://www.jneurosci.org/content/early/2017/03/06/JNEUROSCI.0117-17.2017.full
AB  - While there is growing appreciation for diversity among ventral tegmental area (VTA) dopamine neurons, much less is known regarding functional heterogeneity among substantia nigra (SNc) neurons. Here, we show that calbindin-positive dorsal tier and calbindin-negative ventral tier SNc dopaminergic neurons in mice comprise functionally distinct subpopulations distinguished by their dendritic calcium signaling, rebound excitation, and physiological responses to dopamine D2-receptor (D2) autoinhibition. While dopamine is known to inhibit action potential backpropagation, our experiments revealed an unexpected enhancement of excitatory responses and dendritic calcium signals in the presence of D2-receptor inhibition. Specifically, dopamine inhibition and direct hyperpolarization enabled the generation of low-threshold depolarizations that occurred in an all-or-none or graded manner, due to recruitment of T-type calcium channels. Interestingly, these effects occurred selectively in calbindin-negative dopaminergic neurons within the SNc. Thus, calbindin-positive and negative SNc neurons differ substantially in their calcium channel composition and efficacy of excitatory inputs in the presence of dopamine inhibition.SIGNIFICANCE STATEMENTDopamine neurons in the substantia nigra pars compacta can be divided into two main populations: the calbindin-negative ventral tier, which is highly vulnerable to neurodegeneration in Parkinson's disease, and the calbindin-positive dorsal tier, which is relatively resilient. While tonic firing is similar in these subpopulations, we find that their responses to dopamine inhibition is strikingly different. We see that vulnerable neurons have more T-type calcium current than resilient neurons, which increases their sensitivity to excitatory input during and directly following periods of inhibition. T-type channels drive large dendritic calcium transients in calbindin-negative, but not calbindin-positive neurons and may contribute to their selective vulnerability. Therefore, these subpopulations can differentially transmit dopamine signals even when receiving similar patterns of input.