PMID- 37437920
OWN - NLM
STAT- MEDLINE
DCOM- 20230714
LR  - 20230721
IS  - 1488-2434 (Electronic)
IS  - 1180-4882 (Print)
IS  - 1180-4882 (Linking)
VI  - 48
IP  - 4
DP  - 2023 Jul-Aug
TI  - Involvement of nucleus accumbens D2-medium spiny neurons projecting to the 
      ventral pallidum in anxiety-like behaviour.
PG  - E267-E284
LID - 10.1503/jpn.220111 [doi]
AB  - BACKGROUND: The nucleus accumbens (NAcc) is a crucial brain region for 
      emotionally relevant behaviours. The NAcc is mainly composed of medium spiny 
      neurons (MSNs) expressing either dopamine receptor D1 (D1-MSNs) or D2 (D2-MSNs). 
      The D1-MSNs project to the ventral tegmental area (VTA) and the ventral pallidum 
      (VP), whereas the D2-MSNs project only to the VP. The D1- and D2-MSNs have been 
      associated with depression-like behaviours, but their contribution to anxiety 
      remains to be determined. METHODS: We used optogenetic tools to selectively 
      manipulate D1-MSN projections from the NAcc core to the VP or VTA and D2-MSN 
      projections to the VP during validated anxiety-producing behavioural procedures 
      in naive mice. In addition, we assessed the effects of optical stimulation on 
      neuronal activity using in vivo electrophysiologic recordings in anesthetized 
      animals. RESULTS: Optogenetic activation of D1-MSN projections to the VTA or VP 
      did not trigger anxiety-like behaviour. However, optical activation of D2-MSN 
      projections to the VP significantly increased anxiety-like behaviour. This 
      phenotype was associated with a decrease in the neuronal activity of putative 
      GABAergic neurons in the VP. Importantly, pretreating D2-MSN-VP animals with the 
      gamma-aminobutyric acid modulator diazepam prevented the optically triggered 
      anxiety-like behaviour. LIMITATIONS: The exclusive use of males in the 
      behavioural tests limits broader interpretation of the findings. Although we used 
      optogenetic conditions that trigger quasi-physiologic changes, there are caveats 
      associated with the artificial manipulation of neuronal activity. CONCLUSION: The 
      D2-MSN-VP projections contributed to the development of anxiety-like behaviour, 
      through modulation of GABAergic activity in the VP.
CI  - (c) 2023 CMA Impact Inc. or its licensors.
FAU - Correia, Raquel
AU  - Correia R
AD  - From the Life and Health Sciences Research Institute (ICVS), School of Medicine, 
      University of Minho, Braga, Portugal (Correia, Coimbra, Domingues, Wezik, 
      Vieitas-Gaspar, Gaspar, Sousa, Pinto, Rodrigues, Soares-Cunha); ICVS/3B's-PT 
      Government Associate Laboratory, Braga and Guimaraes, Portugal (Correia, Coimbra, 
      Domingues, Wezik, Vieitas-Gaspar, Gaspar, Sousa, Pinto, Rodrigues, Soares-Cunha); 
      and the Clinical Academic Center - Braga, Braga, Portugal (Sousa, Rodrigues).
FAU - Coimbra, Barbara
AU  - Coimbra B
AD  - From the Life and Health Sciences Research Institute (ICVS), School of Medicine, 
      University of Minho, Braga, Portugal (Correia, Coimbra, Domingues, Wezik, 
      Vieitas-Gaspar, Gaspar, Sousa, Pinto, Rodrigues, Soares-Cunha); ICVS/3B's-PT 
      Government Associate Laboratory, Braga and Guimaraes, Portugal (Correia, Coimbra, 
      Domingues, Wezik, Vieitas-Gaspar, Gaspar, Sousa, Pinto, Rodrigues, Soares-Cunha); 
      and the Clinical Academic Center - Braga, Braga, Portugal (Sousa, Rodrigues).
FAU - Domingues, Ana Veronica
AU  - Domingues AV
AD  - From the Life and Health Sciences Research Institute (ICVS), School of Medicine, 
      University of Minho, Braga, Portugal (Correia, Coimbra, Domingues, Wezik, 
      Vieitas-Gaspar, Gaspar, Sousa, Pinto, Rodrigues, Soares-Cunha); ICVS/3B's-PT 
      Government Associate Laboratory, Braga and Guimaraes, Portugal (Correia, Coimbra, 
      Domingues, Wezik, Vieitas-Gaspar, Gaspar, Sousa, Pinto, Rodrigues, Soares-Cunha); 
      and the Clinical Academic Center - Braga, Braga, Portugal (Sousa, Rodrigues).
FAU - Wezik, Marcelina
AU  - Wezik M
AD  - From the Life and Health Sciences Research Institute (ICVS), School of Medicine, 
      University of Minho, Braga, Portugal (Correia, Coimbra, Domingues, Wezik, 
      Vieitas-Gaspar, Gaspar, Sousa, Pinto, Rodrigues, Soares-Cunha); ICVS/3B's-PT 
      Government Associate Laboratory, Braga and Guimaraes, Portugal (Correia, Coimbra, 
      Domingues, Wezik, Vieitas-Gaspar, Gaspar, Sousa, Pinto, Rodrigues, Soares-Cunha); 
      and the Clinical Academic Center - Braga, Braga, Portugal (Sousa, Rodrigues).
FAU - Vieitas-Gaspar, Natacha
AU  - Vieitas-Gaspar N
AD  - From the Life and Health Sciences Research Institute (ICVS), School of Medicine, 
      University of Minho, Braga, Portugal (Correia, Coimbra, Domingues, Wezik, 
      Vieitas-Gaspar, Gaspar, Sousa, Pinto, Rodrigues, Soares-Cunha); ICVS/3B's-PT 
      Government Associate Laboratory, Braga and Guimaraes, Portugal (Correia, Coimbra, 
      Domingues, Wezik, Vieitas-Gaspar, Gaspar, Sousa, Pinto, Rodrigues, Soares-Cunha); 
      and the Clinical Academic Center - Braga, Braga, Portugal (Sousa, Rodrigues).
FAU - Gaspar, Rita
AU  - Gaspar R
AD  - From the Life and Health Sciences Research Institute (ICVS), School of Medicine, 
      University of Minho, Braga, Portugal (Correia, Coimbra, Domingues, Wezik, 
      Vieitas-Gaspar, Gaspar, Sousa, Pinto, Rodrigues, Soares-Cunha); ICVS/3B's-PT 
      Government Associate Laboratory, Braga and Guimaraes, Portugal (Correia, Coimbra, 
      Domingues, Wezik, Vieitas-Gaspar, Gaspar, Sousa, Pinto, Rodrigues, Soares-Cunha); 
      and the Clinical Academic Center - Braga, Braga, Portugal (Sousa, Rodrigues).
FAU - Sousa, Nuno
AU  - Sousa N
AD  - From the Life and Health Sciences Research Institute (ICVS), School of Medicine, 
      University of Minho, Braga, Portugal (Correia, Coimbra, Domingues, Wezik, 
      Vieitas-Gaspar, Gaspar, Sousa, Pinto, Rodrigues, Soares-Cunha); ICVS/3B's-PT 
      Government Associate Laboratory, Braga and Guimaraes, Portugal (Correia, Coimbra, 
      Domingues, Wezik, Vieitas-Gaspar, Gaspar, Sousa, Pinto, Rodrigues, Soares-Cunha); 
      and the Clinical Academic Center - Braga, Braga, Portugal (Sousa, Rodrigues).
FAU - Pinto, Luisa
AU  - Pinto L
AD  - From the Life and Health Sciences Research Institute (ICVS), School of Medicine, 
      University of Minho, Braga, Portugal (Correia, Coimbra, Domingues, Wezik, 
      Vieitas-Gaspar, Gaspar, Sousa, Pinto, Rodrigues, Soares-Cunha); ICVS/3B's-PT 
      Government Associate Laboratory, Braga and Guimaraes, Portugal (Correia, Coimbra, 
      Domingues, Wezik, Vieitas-Gaspar, Gaspar, Sousa, Pinto, Rodrigues, Soares-Cunha); 
      and the Clinical Academic Center - Braga, Braga, Portugal (Sousa, Rodrigues).
FAU - Rodrigues, Ana Joao
AU  - Rodrigues AJ
AD  - From the Life and Health Sciences Research Institute (ICVS), School of Medicine, 
      University of Minho, Braga, Portugal (Correia, Coimbra, Domingues, Wezik, 
      Vieitas-Gaspar, Gaspar, Sousa, Pinto, Rodrigues, Soares-Cunha); ICVS/3B's-PT 
      Government Associate Laboratory, Braga and Guimaraes, Portugal (Correia, Coimbra, 
      Domingues, Wezik, Vieitas-Gaspar, Gaspar, Sousa, Pinto, Rodrigues, Soares-Cunha); 
      and the Clinical Academic Center - Braga, Braga, Portugal (Sousa, Rodrigues) 
      carinacunha@med.uminho.pt ajrodrigues@med.uminho.pt.
FAU - Soares-Cunha, Carina
AU  - Soares-Cunha C
AD  - From the Life and Health Sciences Research Institute (ICVS), School of Medicine, 
      University of Minho, Braga, Portugal (Correia, Coimbra, Domingues, Wezik, 
      Vieitas-Gaspar, Gaspar, Sousa, Pinto, Rodrigues, Soares-Cunha); ICVS/3B's-PT 
      Government Associate Laboratory, Braga and Guimaraes, Portugal (Correia, Coimbra, 
      Domingues, Wezik, Vieitas-Gaspar, Gaspar, Sousa, Pinto, Rodrigues, Soares-Cunha); 
      and the Clinical Academic Center - Braga, Braga, Portugal (Sousa, Rodrigues) 
      carinacunha@med.uminho.pt ajrodrigues@med.uminho.pt.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230712
PL  - Canada
TA  - J Psychiatry Neurosci
JT  - Journal of psychiatry & neuroscience : JPN
JID - 9107859
SB  - IM
MH  - Male
MH  - Animals
MH  - Mice
MH  - *Nucleus Accumbens
MH  - Medium Spiny Neurons
MH  - *Basal Forebrain
MH  - Anxiety
MH  - Anxiety Disorders
PMC - PMC10356001
COIS- Competing interests: None declared.
EDAT- 2023/07/13 01:06
MHDA- 2023/07/14 13:06
PMCR- 2023/07/12
CRDT- 2023/07/12 20:43
PHST- 2022/06/27 00:00 [received]
PHST- 2022/12/13 00:00 [revised]
PHST- 2023/01/10 00:00 [revised]
PHST- 2023/01/11 00:00 [accepted]
PHST- 2023/07/14 13:06 [medline]
PHST- 2023/07/13 01:06 [pubmed]
PHST- 2023/07/12 20:43 [entrez]
PHST- 2023/07/12 00:00 [pmc-release]
AID - 48/4/E267 [pii]
AID - 48-4-E267 [pii]
AID - 10.1503/jpn.220111 [doi]
PST - epublish
SO  - J Psychiatry Neurosci. 2023 Jul 12;48(4):E267-E284. doi: 10.1503/jpn.220111. 
      Print 2023 Jul-Aug.