PMID- 32447811
OWN - NLM
STAT- MEDLINE
DCOM- 20210716
LR  - 20210716
IS  - 1601-183X (Electronic)
IS  - 1601-1848 (Print)
IS  - 1601-183X (Linking)
VI  - 19
IP  - 6
DP  - 2020 Jul
TI  - Hippocampal knockdown of alpha2 nicotinic or M1 muscarinic acetylcholine receptors in 
      C57BL/6J male mice impairs cued fear conditioning.
PG  - e12677
LID - 10.1111/gbb.12677 [doi]
AB  - Acetylcholine (ACh) signaling in the hippocampus is important for behaviors 
      related to learning, memory and stress. In this study, we investigated the role 
      of two ACh receptor subtypes previously shown to be involved in fear and anxiety, 
      the M1 mAChR and the alpha2 nAChR, in mediating the effects of hippocampal ACh on 
      stress-related behaviors. Adeno-associated viral vectors containing short-hairpin 
      RNAs targeting M1 or alpha2 were infused into the hippocampus of male C57BL/6J mice, 
      and behavior in a number of paradigms related to stress responses and fear 
      learning was evaluated. There were no robust effects of hippocampal M1 mAChR or 
      alpha2 nAChR knockdown (KD) in the light/dark box, tail suspension, forced swim or 
      novelty-suppressed feeding tests. However, effects on fear learning were observed 
      in both KD groups. Short term learning was intact immediately after training in 
      all groups of mice, but both the M1 and alpha2 hippocampal knock down resulted in 
      impaired cued fear conditioning 24 h after training. In addition, there was a 
      trend for a deficit in contextual memory the M1 mAChR KD group 24 h after 
      training. These results suggest that alpha2 nicotinic and M1 muscarinic ACh receptors 
      in the hippocampus contribute to fear learning and could be relevant targets to 
      modify brain circuits involved in stress-induced reactivity to associated cues.
CI  - (c) 2020 John Wiley & Sons Ltd and International Behavioural and Neural Genetics 
      Society.
FAU - Mineur, Yann S
AU  - Mineur YS
AD  - Department of Psychiatry, Yale University School of Medicine, New Haven, 
      Connecticut, USA.
FAU - Ernstsen, Charlotte
AU  - Ernstsen C
AD  - Department of Psychiatry, Yale University School of Medicine, New Haven, 
      Connecticut, USA.
FAU - Islam, Ashraful
AU  - Islam A
AD  - Department of Psychiatry, Yale University School of Medicine, New Haven, 
      Connecticut, USA.
FAU - Lefoli Maibom, Kathrine
AU  - Lefoli Maibom K
AD  - Department of Psychiatry, Yale University School of Medicine, New Haven, 
      Connecticut, USA.
FAU - Picciotto, Marina R
AU  - Picciotto MR
AUID- ORCID: 0000-0002-4404-1280
AD  - Department of Psychiatry, Yale University School of Medicine, New Haven, 
      Connecticut, USA.
LA  - eng
GR  - R01 MH077681/MH/NIMH NIH HHS/United States
GR  - DA036151/DA/NIDA NIH HHS/United States
GR  - U54 DA036151/DA/NIDA NIH HHS/United States
GR  - AA027989/AA/NIAAA NIH HHS/United States
GR  - U54 AA027989/AA/NIAAA NIH HHS/United States
GR  - DP1 DA050986/DA/NIDA NIH HHS/United States
GR  - P50 DA036151/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - England
TA  - Genes Brain Behav
JT  - Genes, brain, and behavior
JID - 101129617
RN  - 0 (CHRNA2 protein, mouse)
RN  - 0 (Receptor, Muscarinic M1)
RN  - 0 (Receptors, Nicotinic)
SB  - IM
EIN - Genes Brain Behav. 2020 Sep;19(7):e12693. PMID: 32909690
MH  - Animals
MH  - *Conditioning, Operant
MH  - Cues
MH  - *Fear
MH  - Gene Deletion
MH  - HEK293 Cells
MH  - Hippocampus/*metabolism/physiology
MH  - Humans
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Receptor, Muscarinic M1/*genetics
MH  - Receptors, Nicotinic/*genetics
PMC - PMC8018799
MID - NIHMS1684686
OTO - NOTNLM
OT  - acetylcholine
OT  - behavior
OT  - fear learning
OT  - hippocampus
OT  - mAChR
OT  - mouse
OT  - muscarinic
OT  - nAChR
OT  - nicotinic
OT  - shRNA
EDAT- 2020/05/25 06:00
MHDA- 2021/07/17 06:00
PMCR- 2021/07/01
CRDT- 2020/05/25 06:00
PHST- 2020/04/13 00:00 [received]
PHST- 2020/05/19 00:00 [revised]
PHST- 2020/05/21 00:00 [accepted]
PHST- 2020/05/25 06:00 [pubmed]
PHST- 2021/07/17 06:00 [medline]
PHST- 2020/05/25 06:00 [entrez]
PHST- 2021/07/01 00:00 [pmc-release]
AID - 10.1111/gbb.12677 [doi]
PST - ppublish
SO  - Genes Brain Behav. 2020 Jul;19(6):e12677. doi: 10.1111/gbb.12677.