Astrocytic Control of Midbrain Dopamine Neurons
The midbrain dopaminergic system originates in the SNc and the VTA. Together, they make of the majority of the dopamine production in the CNS and are involved in processing a wide range of behaviors including rewarding and aversive stimuli. Prior research has focused on the role of neurons in coordinating behavioral outcomes. However, whether astrocytes influence local neuronal communication remained unexplored.
Using slice electrophysiology, optogenetics, pharmacological manipulations, and different behavioral assays, I was able to determine that astrocytes are an important contributor in the processing of rewarding and aversive stimuli. I hypothesized that astrocytes have the ability to control the dopaminergic activity by controlling the extracellular concentrations of different neurotransmitters. My experiments determined that astrocytes control dopamine neuron burst firing, an important signal involved in rewarding stimuli, by regulating the extracellular glycine concentration at NMDA receptor synapses in the SNc. I also determined that selective activation of VTA astrocytes increased afferent-driven glutamatergic excitation of local GABA neurons via the glutamate transporter-1. The increased excitation of local GABA neurons elicited a subsequent increase in inhibition of VTA dopamine neurons that drove avoidance behavior, elicited learned avoidance of cues associated with avoidance, and occluded learned preference for cues associated with reward. Thus, midbrain astrocytes recruit active circuit-delimited neuronal inputs to balance expression of learned approach and avoidance behaviors.