A Comparison of Dopaminergic and Cholinergic Populations Reveals Unique Contributions of VTA Dopamine Neurons to Short-Term Memory
Jung Yoon Choi,
Hee Jae Jang,
Sharon Ornelas,
Weston T. Fleming,
Daniel Fürth,
Jennifer Au,
Akhil Bandi,
Esteban A. Engel,
Ilana B. Witten
Affiliations
Jung Yoon Choi
Princeton Neuroscience Institute, Princeton University, Princeton, NJ 08544, USA; Department of Psychology, Princeton University, Princeton, NJ 08544, USA
Hee Jae Jang
Princeton Neuroscience Institute, Princeton University, Princeton, NJ 08544, USA
Sharon Ornelas
Princeton Neuroscience Institute, Princeton University, Princeton, NJ 08544, USA
Weston T. Fleming
Princeton Neuroscience Institute, Princeton University, Princeton, NJ 08544, USA
Daniel Fürth
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA
Jennifer Au
Princeton Neuroscience Institute, Princeton University, Princeton, NJ 08544, USA
Akhil Bandi
Princeton Neuroscience Institute, Princeton University, Princeton, NJ 08544, USA
Esteban A. Engel
Princeton Neuroscience Institute, Princeton University, Princeton, NJ 08544, USA
Ilana B. Witten
Princeton Neuroscience Institute, Princeton University, Princeton, NJ 08544, USA; Department of Psychology, Princeton University, Princeton, NJ 08544, USA; Corresponding author
Summary: We systematically compare the contributions 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 relate to performance with an inverted-U, despite the fact that both populations have low activity during that time. Transient manipulations reveal that only VTA-DA neurons, and not the other three populations we examine, contribute causally and selectively to short-term memory. This contribution is most significant during the delay period, when both increases and decreases in VTA-DA activity impair 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, and they also provide support for classic ideas about an inverted-U relationship between neuromodulation and cognition.