A Comparison of Dopaminergic and Cholinergic Populations Reveals Unique Contributions of VTA Dopamine Neurons to Short-Term Memory

Cell Rep. 2020 Dec 15;33(11):108492. doi: 10.1016/j.celrep.2020.108492.


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.

Keywords: Inverted-U; Medial septum; Neuromodulation; Nucleus basalis; SNc; Short-term memory; VTA; Working memory; acetylcholine; dopamine.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cholinergic Neurons / metabolism*
  • Dopaminergic Neurons / metabolism*
  • Humans
  • Male
  • Memory, Short-Term / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Ventral Tegmental Area / physiology