A comparison of dopaminergic and cholinergic populations reveals unique contributions of VTA dopamine neurons to short-term memory

We systematically compared the contribution of two dopaminergic and two cholinergic ascending populations to a spatial short-term memory task in rats. In ventral tegmental area dopamine (VTA-DA) and nucleus basalis cholinergic (NB-ChAT) populations, trial-by-trial fluctuations in activity during the delay period related to performance with an inverted-U, despite the fact that both populations had low activity during that time. Transient manipulations revealed that only VTA-DA neurons, and not the other three populations we examined, contributed causally and selectively to short-term memory. This contribution was most significant during the delay period, when both increases or decreases in VTA-DA activity impaired short-term memory. Our results reveal a surprising dissociation between when VTA-DA neurons are most active and when they have the biggest causal contribution to short-term memory, while also providing new types of support for classic ideas about an inverted-U relationship between neuromodulation and cognition.