Constraints on the subsecond modulation of striatal dynamics by physiological dopamine signaling

Dopaminergic neurons play a crucial role in associative learning, but their capacity to regulate behavior on subsecond timescales remains debated. It is thought that dopaminergic neurons drive certain behaviors by rapidly modulating striatal spiking activity; however, a view has emerged that only artificially high (that is, supra-physiological) dopamine signals alter behavior on fast timescales. This raises the possibility that moment-to-moment striatal spiking activity is not strongly shaped by dopamine signals in the physiological range. To test this, we transiently altered dopamine levels while monitoring spiking responses in the ventral striatum of behaving mice. These manipulations led to only weak changes in striatal activity, except when dopamine release exceeded reward-matched levels. These findings suggest that dopaminergic neurons normally play a minor role in the subsecond modulation of striatal dynamics in relation to other inputs and demonstrate the importance of discerning dopaminergic neuron contributions to brain function under physiological and potentially nonphysiological conditions. The role of dopaminergic neurons in modulating striatal dynamics on subsecond timescales remains unclear. Long, Lee et al. show that only potentially supra-physiological dopamine levels are capable of strongly and rapidly altering striatal spiking activity.