Prefrontal cortex-driven dopamine signals in the striatum show unique spatial and pharmacological properties

Martín F. Adrover, Jung Hoon Shin, Cesar Quiroz, Sergi Ferré, Julia C. Lemos, Veronica A. Alvarez

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


Dopamine (DA) signals in the striatum are critical for a variety of vital processes, including motivation, motor learning, and reinforcement learning. Striatal DA signals can be evoked by direct activation of inputs from midbrain DA neurons (DANs) as well as cortical and thalamic inputs to the striatum. In this study, we show that in vivo optogenetic stimulation of prelimbic (PrL) and infralimbic (IL) cortical afferents to the striatum triggers an increase in extracellular DA concentration, which coincides with elevation of striatal acetylcholine (ACh) levels. This increase is blocked by a nicotinic ACh receptor (nAChR) antagonist. Using single or dual optogenetic stimulation in brain slices from male and female mice, we compared the properties of these PrL/IL-evoked DA signals with those evoked by stimulation from midbrain DAN axonal projections. PrL/IL-evoked DA signals are undistinguishable from DAN evoked DA signals in their amplitudes and electrochemical properties. However, PrL/IL-evoked DA signals are spatially restricted and preferentially recorded in the dorsomedial striatum. PrL/IL-evoked DA signals also differ in their pharmacological properties, requiring activation of glutamate and nicotinic ACh receptors. Thus, both in vivo and in vitro results indicate that cortical evoked DA signals rely on recruitment of cholinergic interneurons, which renders DA signals less able to summate during trains of stimulation and more sensitive to both cholinergic drugs and temperature. In conclusion, cortical and midbrain inputs to the striatum evoke DA signals with unique spatial and pharmacological properties that likely shape their functional roles and behavioral relevance. SIGNIFICANCE STATEMENT Dopamine signals in the striatum play a critical role in basal ganglia function, such as reinforcement and motor learning. Different afferents to the striatum can trigger dopamine signals, but their release properties are not well understood. Further, these input-specific dopamine signals have only been studied in separate animals. Here we show that optogenetic stimulation of cortical glutamatergic afferents to the striatum triggers dopamine signals both in vivo and in vitro These afferents engage cholinergic interneurons, which drive dopamine release from dopamine neuron axons by activation of nicotinic acetylcholine receptors. We also show that cortically evoked dopamine signals have other unique properties, including spatial restriction and sensitivity to temperature changes than dopamine signals evoked by stimulation of midbrain dopamine neuron axons.

Original languageEnglish (US)
Pages (from-to)7510-7522
Number of pages13
JournalJournal of Neuroscience
Issue number39
StatePublished - Sep 23 2020

Bibliographical note

Funding Information:
Received May 27, 2020; revised July 22, 2020; accepted Aug. 17, 2020. Author contributions: M.F.A., J.H.S., and V.A.A. designed research; M.F.A., J.H.S., C.Q., S.F., and J.C.L. performed research; M.F.A., J.H.S., C.Q., S.F., and J.C.L. analyzed data; M.F.A., J.H.S., and V.A.A. wrote the first draft of the paper; M.F.A., J.H.S., C.Q., S.F., J.C.L., and V.A.A. edited the paper; M.F.A., J.H.S., and V.A.A. wrote the paper. *M.F.A. and J.H.S. contributed equally to this work. This work was supported by the Intramural Programs of National Institute on Alcohol Abuse and Alcoholism, National Institute of Neurological Disorders and Stroke (ZIA-AA000421), and National Institute on Drug Abuse. We thank Roland Bock (National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health) for development of the VIGOR acquisition and analysis software; Drs. Karl Deisseroth (Stanford University) and Ed Boyden for providing the channelrhodopsin-2 and ChrimsonR constructs, respectively; and members of the A.A.V. laboratory for valuable comments on the manuscript. M.F. Adrover’s present address: Instituto de Investigaciones en Ingeniería Genética y Biología Molecular, CONICET, Buenos Aires, C1428ADN, Argentina. J.C. Lemos’ present address: Department of Neuroscience, University of Minnesota, Minneapolis, Minnesota 55455. The authors declare no competing financial interests. Correspondence should be addressed to Veronica A. Alvarez at Copyright © 2020 the authors

Publisher Copyright:
© 2020 the authors.


  • DA release
  • Dorsomedial striatum
  • Fast-scan cyclic voltammetry
  • Optogenetics
  • PFC


Dive into the research topics of 'Prefrontal cortex-driven dopamine signals in the striatum show unique spatial and pharmacological properties'. Together they form a unique fingerprint.

Cite this