PMID- 31031594
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 1662-5102 (Print)
IS  - 1662-5102 (Electronic)
IS  - 1662-5102 (Linking)
VI  - 13
DP  - 2019
TI  - Accumbal Adenosine A(2A) Receptors Enhance Cognitive Flexibility by Facilitating 
      Strategy Shifting.
PG  - 130
LID - 10.3389/fncel.2019.00130 [doi]
LID - 130
AB  - The deficits of cognitive flexibility (including attentional set-shifting and 
      reversal learning) concomitant with dysfunction of the striatum are observed in 
      several neuropsychiatric disorders. Rodent and human studies have identified the 
      striatum [particularly the dorsomedial striatum (DMS) and nucleus accumbens 
      (NAc)] as the critical locus for control of cognitive flexibility, but the 
      effective neuromodulator and pharmacological control of cognitive flexibility 
      remains to be determined. The adenosine A(2A) receptors (A(2A)Rs) are highly 
      enriched in the striatopallidal neurons where they integrate dopamine and 
      glutamate signals to modulate several cognitive behaviors, but their contribution 
      to cognitive flexibility control is unclear. In this study, by coupling an 
      automated operant cognitive flexibility task with striatal subregional knockdown 
      (KD) of the A(2A)R via the Cre-loxP strategy, we demonstrated that NAc A(2A)R KD 
      improved cognitive flexibility with enhanced attentional set-shifting and 
      reversal learning by decreasing regressive and perseverative errors, 
      respectively. This facilitation was not attributed to mnemonic process or motor 
      activity as NAc A(2A)R KD did not affect the visual discrimination, 
      lever-pressing acquisition, and locomotor activity, but was associated with 
      increased attention and motivation as evident by the progressive ratio test 
      (PRT). In contrast to NAc A(2A)Rs, DMS A(2A)Rs KD neither affected visual 
      discrimination nor improved set-shifting nor reversal learning, but promoted the 
      effort-related motivation. Thus, NAc and DMS A(2A)Rs exert dissociable controls 
      of cognitive flexibility with NAc A(2A)Rs KD selectively enhancing cognitive 
      flexibility by facilitating strategy shifting with increased 
      motivation/attention.
FAU - Zhou, Jianhong
AU  - Zhou J
AD  - Molecular Neuropharmacology Laboratory, School of Optometry and Ophthalmology and 
      Eye Hospital, Wenzhou Medical University, Wenzhou, China.
AD  - State Key Laboratory of Optometry & Vision Science, Wenzhou, China.
FAU - Wu, Beibei
AU  - Wu B
AD  - Molecular Neuropharmacology Laboratory, School of Optometry and Ophthalmology and 
      Eye Hospital, Wenzhou Medical University, Wenzhou, China.
AD  - State Key Laboratory of Optometry & Vision Science, Wenzhou, China.
FAU - Lin, Xiangxiang
AU  - Lin X
AD  - Molecular Neuropharmacology Laboratory, School of Optometry and Ophthalmology and 
      Eye Hospital, Wenzhou Medical University, Wenzhou, China.
AD  - State Key Laboratory of Optometry & Vision Science, Wenzhou, China.
FAU - Dai, Yuwei
AU  - Dai Y
AD  - Molecular Neuropharmacology Laboratory, School of Optometry and Ophthalmology and 
      Eye Hospital, Wenzhou Medical University, Wenzhou, China.
AD  - State Key Laboratory of Optometry & Vision Science, Wenzhou, China.
FAU - Li, Tingting
AU  - Li T
AD  - Molecular Neuropharmacology Laboratory, School of Optometry and Ophthalmology and 
      Eye Hospital, Wenzhou Medical University, Wenzhou, China.
AD  - State Key Laboratory of Optometry & Vision Science, Wenzhou, China.
FAU - Zheng, Wu
AU  - Zheng W
AD  - Molecular Neuropharmacology Laboratory, School of Optometry and Ophthalmology and 
      Eye Hospital, Wenzhou Medical University, Wenzhou, China.
AD  - State Key Laboratory of Optometry & Vision Science, Wenzhou, China.
FAU - Guo, Wei
AU  - Guo W
AD  - Molecular Neuropharmacology Laboratory, School of Optometry and Ophthalmology and 
      Eye Hospital, Wenzhou Medical University, Wenzhou, China.
AD  - State Key Laboratory of Optometry & Vision Science, Wenzhou, China.
FAU - Vakal, Sergii
AU  - Vakal S
AD  - Molecular Neuropharmacology Laboratory, School of Optometry and Ophthalmology and 
      Eye Hospital, Wenzhou Medical University, Wenzhou, China.
FAU - Chen, Xingjun
AU  - Chen X
AD  - Molecular Neuropharmacology Laboratory, School of Optometry and Ophthalmology and 
      Eye Hospital, Wenzhou Medical University, Wenzhou, China.
AD  - State Key Laboratory of Optometry & Vision Science, Wenzhou, China.
FAU - Chen, Jiang-Fan
AU  - Chen JF
AD  - Molecular Neuropharmacology Laboratory, School of Optometry and Ophthalmology and 
      Eye Hospital, Wenzhou Medical University, Wenzhou, China.
AD  - State Key Laboratory of Optometry & Vision Science, Wenzhou, China.
LA  - eng
PT  - Journal Article
DEP - 20190411
PL  - Switzerland
TA  - Front Cell Neurosci
JT  - Frontiers in cellular neuroscience
JID - 101477935
PMC - PMC6470273
OTO - NOTNLM
OT  - adenosine A2A receptors
OT  - attention
OT  - attentional set-shifting
OT  - dorsomedial striatum
OT  - motivation
OT  - nucleus accumbens
OT  - reversal learning
EDAT- 2019/04/30 06:00
MHDA- 2019/04/30 06:01
PMCR- 2019/01/01
CRDT- 2019/04/30 06:00
PHST- 2019/02/16 00:00 [received]
PHST- 2019/03/14 00:00 [accepted]
PHST- 2019/04/30 06:00 [entrez]
PHST- 2019/04/30 06:00 [pubmed]
PHST- 2019/04/30 06:01 [medline]
PHST- 2019/01/01 00:00 [pmc-release]
AID - 10.3389/fncel.2019.00130 [doi]
PST - epublish
SO  - Front Cell Neurosci. 2019 Apr 11;13:130. doi: 10.3389/fncel.2019.00130. 
      eCollection 2019.