UCLA

While the crucial role of dopaminergic (DA) neurons in associative learning is firmly established, there is less consensus about whether they also play a major regulatory function in behavioral control on short, subsecond timescales. Mechanistically, it is thought that DA neurons drive such behaviors by rapidly modulating striatal spiking activity – an effect whose magnitude is based on incomplete evidence. However, a view has emerged that only artificially high (i.e., supra-physiological) DA signals can robustly alter behavioral performance on fast timescales. This raises the intriguing possibility that moment-to-moment striatal spiking activity is actually not strongly shaped by DA signals in the physiological regime. To test this, we monitored spiking responses in the ventral striatum of behaving mice, while transiently raising or lowering DA levels. Surprisingly, most of these manipulations led to only weak changes in striatal activity, with the notable exception of when DA release exceeded reward-matched levels. These findings suggest that in contrast to the widely held assumption, DA neurons normally play only a minor function in the rapid control of striatal dynamics in relation to other inputs. This constrained role demonstrates the importance of discerning DA neuron contributions to brain function under physiological and potentially non-physiological conditions.