Connectomic dopamine-neuron disinhibition accelerates behavioral extinction

Abstract

Animals must balance persistence with flexibility when outcomes change. Behavioral extinction--the reduction in responding to cues that no longer predict reward--is widely thought to be driven by pauses in dopamine-neuron firing upon omission of expected rewards. However, whether these pauses are necessary remains unknown. We used a connectomic intervention to weaken inhibitory synapses onto dopamine neurons in the ventral tegmental area, attenuating electrophysiologically defined pauses while sparing tonic and burst firing. Contrary to canonical accounts, this intervention accelerated rather than delayed behavioral extinction, demonstrating that these synapses normally postpone behavioral extinction. Learning about a newly rewarded cue was spared, arguing against a general disruption of learning. Dopamine photometry showed that the intervention attenuated reward-omission dopamine dips, whose dissipation preceded and predicted behavioral extinction across mice. These findings show that pause-generating inhibitory inputs to dopamine neurons sustain behavioral persistence. This mechanism may protect established associations from premature abandonment as outcomes fluctuate.