Dynamics of burst synchronization induced by excitatory inputs on midbrain dopamine neurons
Dopamine (DA) signals play critical roles in reward-related behavior, decision making, and learning. Yet the mainstream notion that DA signals are encoded by the temporal dynamics of individual DA cell activity is increasingly contested with data supporting that DA signals prefer to be encoded by the spatial organization of DA neuron populations. However, how distributed and parallel excitatory afferent inputs simultaneously induce burst synchronization (BS) is unclear. Our previous work implies that the burst could presumably transition from an integrator to a resonator if the excitatory inputs increase further. Here the responses of networked DA neurons to different intensity of excitatory inputs are investigated. It is found that as NMDA conductance increases, the network will transition from resting state to burst asynchronization (BA) state and then to BS state, showing a bounded BA and BS region in the NMDA conductance space. Furthermore, it is found that as muscarinic receptors modulated Ca2+ dependent cationic (CAN) conductance increases, both boundaries between resting and BA, and between BA and BS gradually decrease. Phase plane analysis on DA reduced model unveils that the burst transition to a resonator underpins the changes in the network dynamics. Slow-fast dissection analysis on DA full model uncovers that the underlying mechanism of the roles and synergy of NMDA and muscarinic receptors in inducing the burst transition emerge from the enlargement of nonlinear positive feedback relationship between more Ca2+ influx provided by additional NMDA current and more ICAN modulated by added muscarinic receptors. Moreover, the lag in DA volume transmission has no effect on excitatory inputs-elicited resonator BS except for requiring more excitatory inputs. These findings shed new lights on understanding the collective behavior of DA cells population regulated by the distributed excitatory inputs, and might provide a new perspective for understanding the abnormal DA release in pathological states. Author summaryThe importance of DA signals is beyond doubt, so their encoding mechanism has very important biological significance and draws widespread attention. Yet the mainstream notion that DA cells individual provide a uniform, broadly distributed signal is increasingly contested with data supporting both homogeneity across dopamine cell activity and diversity in DA signals in target regions. Our article proposes that diverse distributed and parallel excitatory inputs can not only regulate the temporal dynamics of individual DA cell activity, but also simultaneously and synergistically regulate the network dynamics of DA cell populations by changing the local dynamics of DA cells, namely the burst transition from integrators to resonators. According to our perspective, many data that are difficult to interpret by the notion of the DA neuron individual coding can be well explained, such as burst asynchronization coding DA ramping signals, the scale of burst synchronization coding the amplitude of phase DA release, inhibitory DA autoreceptors facilitating resonator burst synchronization by postinhibitory rebound, etc. This study aims to elucidate the working mechanism of the DA system in physiological states such as positive reinforcement, and then to provide a new research perspective and foundation for understanding the abnormal DA release in pathological states.