PMID- 34103400
OWN - NLM
STAT- MEDLINE
DCOM- 20211203
LR  - 20240226
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 118
IP  - 24
DP  - 2021 Jun 15
TI  - Selective filtering of excitatory inputs to nucleus accumbens by dopamine and 
      serotonin.
LID - 10.1073/pnas.2106648118 [doi]
LID - e2106648118
AB  - The detailed mechanisms by which dopamine (DA) and serotonin (5-HT) act in the 
      nucleus accumbens (NAc) to influence motivated behaviors in distinct ways remain 
      largely unknown. Here, we examined whether DA and 5-HT selectively modulate 
      excitatory synaptic transmission in NAc medium spiny neurons in an input-specific 
      manner. DA reduced excitatory postsynaptic currents (EPSCs) generated by 
      paraventricular thalamus (PVT) inputs but not by ventral hippocampus (vHip), 
      basolateral amygdala (BLA), or medial prefrontal cortex (mPFC) inputs. In 
      contrast, 5-HT reduced EPSCs generated by inputs from all areas except the mPFC. 
      Release of endogenous DA and 5-HT by methamphetamine (METH) and 
      (+/-)3,4-methylenedioxymethamphetamine (MDMA), respectively, recapitulated these 
      input-specific synaptic effects. Optogenetic inhibition of PVT inputs enhanced 
      cocaine-conditioned place preference, whereas mPFC input inhibition reduced the 
      enhancement of sociability elicited by MDMA. These findings suggest that the 
      distinct, input-specific filtering of excitatory inputs in the NAc by DA and 5-HT 
      contribute to their discrete behavioral effects.
FAU - Christoffel, Daniel J
AU  - Christoffel DJ
AUID- ORCID: 0000-0002-6303-5134
AD  - Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, 
      Stanford University, Stanford, CA 94305.
FAU - Walsh, Jessica J
AU  - Walsh JJ
AUID- ORCID: 0000-0001-8466-8451
AD  - Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, 
      Stanford University, Stanford, CA 94305.
FAU - Hoerbelt, Paul
AU  - Hoerbelt P
AUID- ORCID: 0000-0002-8707-5376
AD  - Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, 
      Stanford University, Stanford, CA 94305.
FAU - Heifets, Boris D
AU  - Heifets BD
AD  - Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, 
      Stanford University, Stanford, CA 94305.
AD  - Department of Anesthesiology, Perioperative and Pain Medicine, Stanford 
      University School of Medicine, Stanford, CA 94305.
FAU - Llorach, Pierre
AU  - Llorach P
AD  - Department of Anesthesiology, Perioperative and Pain Medicine, Stanford 
      University School of Medicine, Stanford, CA 94305.
FAU - Lopez, Ricardo C
AU  - Lopez RC
AUID- ORCID: 0000-0002-1136-9511
AD  - Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, 
      Stanford University, Stanford, CA 94305.
FAU - Ramakrishnan, Charu
AU  - Ramakrishnan C
AD  - Department of Bioengineering, Stanford University, Stanford, CA 94305.
FAU - Deisseroth, Karl
AU  - Deisseroth K
AD  - Department of Bioengineering, Stanford University, Stanford, CA 94305.
AD  - Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, 
      CA 94305.
AD  - HHMI, Stanford University, Stanford, CA 94305.
FAU - Malenka, Robert C
AU  - Malenka RC
AUID- ORCID: 0000-0002-5428-5211
AD  - Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, 
      Stanford University, Stanford, CA 94305; malenka@stanford.edu.
LA  - eng
GR  - K99 DK115895/DK/NIDDK NIH HHS/United States
GR  - P50 DA042012/DA/NIDA NIH HHS/United States
GR  - F32 MH115668/MH/NIMH NIH HHS/United States
GR  - T32 DA035165/DA/NIDA NIH HHS/United States
GR  - K08 MH110610/MH/NIMH NIH HHS/United States
GR  - R00 DK115895/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 333DO1RDJY (Serotonin)
RN  - 44RAL3456C (Methamphetamine)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - Animals
MH  - Behavior, Animal/drug effects
MH  - Dopamine/*pharmacology
MH  - *Excitatory Postsynaptic Potentials/drug effects
MH  - Methamphetamine/pharmacology
MH  - Mice, Inbred C57BL
MH  - N-Methyl-3,4-methylenedioxyamphetamine/pharmacology
MH  - Neurons/drug effects/physiology
MH  - Nucleus Accumbens/drug effects/*physiology
MH  - Serotonin/*pharmacology
MH  - Social Interaction/drug effects
MH  - Synaptic Transmission/drug effects
MH  - Mice
PMC - PMC8214692
OTO - NOTNLM
OT  - dopamine
OT  - neuromodulators
OT  - nucleus accumbens
OT  - reward
OT  - serotonin
COIS- Competing interest statement: R.C.M. is on the scientific advisory boards for 
      MapLight Therapeutics and MindMed. K.D. is on the scientific advisory board of 
      MapLight Therapeutics.
EDAT- 2021/06/10 06:00
MHDA- 2021/12/15 06:00
PMCR- 2021/12/08
CRDT- 2021/06/09 05:53
PHST- 2021/06/09 05:53 [entrez]
PHST- 2021/06/10 06:00 [pubmed]
PHST- 2021/12/15 06:00 [medline]
PHST- 2021/12/08 00:00 [pmc-release]
AID - 2106648118 [pii]
AID - 202106648 [pii]
AID - 10.1073/pnas.2106648118 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2021 Jun 15;118(24):e2106648118. doi: 
      10.1073/pnas.2106648118.