Distinct Subthreshold Signatures of Midbrain Dopamine Neurons Drive Firing Patterns During Noxious Events

Midbrain dopamine neurons are strongly implicated in reward and aversion. Aversive stimuli are encoded by the firing pattern of dopamine neurons, which governs when dopamine is released at target regions. A response to an aversive stimulus is generated by integrating activity from multiple afferents, and changes in dopamine neuron firing activity are the result of dynamic changes in synaptic input. Using intracellular in vivo recordings, I was able to characterize the subthreshold signatures that elicit either an increase or decrease in dopamine firing activity. A spontaneous increase in dopamine neuron firing activity occurred via two distinct subthreshold mechanisms: 1) A large hyperpolarization followed by a rebound burst; and 2) a transient depolarization and plateau burst. Subthreshold responses evoked by a noxious foot shock were then characterized as either: 1) a large hyperpolarization during a pause in firing, 2) a depolarization during a phasic increase in firing, and 3) a large hyperpolarization followed by a rebound increase in firing activity. Determining the underlying biophysical mechanisms mediating changes in firing pattern provides insight into the afferents that elicit a response during a foot shock.