Matches in SemOpenAlex for { <https://semopenalex.org/work/W4319265493> ?p ?o ?g. }
- W4319265493 abstract "Dopamine system dysfunction is commonly implicated in adolescent-onset neuropsychiatric disorders. Although psychosis symptoms can be alleviated by antipsychotics, cognitive symptoms remain unresponsive to such pharmacological treatments and novel research paradigms investigating the circuit substrates underlying cognitive deficits are critically needed. The frontal cortex and its dopaminergic input from the midbrain are implicated in cognitive functions and undergo maturational changes during adolescence. Here, we used mice carrying mutations in the Arc or DISC1 genes to model mesofrontal dopamine circuit deficiencies and test circuit-based neurostimulation strategies to restore cognitive functions. We found that in a memory-guided spatial navigation task, frontal cortical neurons were activated coordinately at the decision-making point in wild-type but not Arc mutant mice. Chemogenetic stimulation of midbrain dopamine neurons or optogenetic stimulation of frontal cortical dopamine axons in a limited adolescent period consistently reversed genetic defects in mesofrontal innervation, task-coordinated neuronal activity, and memory-guided decision-making at adulthood. Furthermore, adolescent stimulation of dopamine neurons also reversed the same cognitive deficits in DISC1 mutant mice. Our findings reveal common mesofrontal circuit alterations underlying the cognitive deficits caused by two different genes and demonstrate the feasibility of adolescent neurostimulation to reverse these circuit and behavioral deficits. These results may suggest developmental windows and circuit targets for treating cognitive deficits in neurodevelopmental disorders." @default.
- W4319265493 created "2023-02-06" @default.
- W4319265493 creator A5003720683 @default.
- W4319265493 creator A5008366275 @default.
- W4319265493 creator A5009183873 @default.
- W4319265493 creator A5030121920 @default.
- W4319265493 creator A5042419038 @default.
- W4319265493 creator A5043595250 @default.
- W4319265493 creator A5050123380 @default.
- W4319265493 creator A5073494269 @default.
- W4319265493 creator A5078133232 @default.
- W4319265493 creator A5087466819 @default.
- W4319265493 date "2023-02-04" @default.
- W4319265493 modified "2023-10-15" @default.
- W4319265493 title "Adolescent neurostimulation of dopamine circuit reverses genetic deficits in frontal cortex function" @default.
- W4319265493 cites W1467702212 @default.
- W4319265493 cites W1480121462 @default.
- W4319265493 cites W1529892095 @default.
- W4319265493 cites W1584279891 @default.
- W4319265493 cites W1585013154 @default.
- W4319265493 cites W1603381174 @default.
- W4319265493 cites W1603591159 @default.
- W4319265493 cites W1614219830 @default.
- W4319265493 cites W1870304014 @default.
- W4319265493 cites W1875506666 @default.
- W4319265493 cites W1905338895 @default.
- W4319265493 cites W1939041013 @default.
- W4319265493 cites W1964516189 @default.
- W4319265493 cites W1966343623 @default.
- W4319265493 cites W1968461255 @default.
- W4319265493 cites W1969275478 @default.
- W4319265493 cites W1971055770 @default.
- W4319265493 cites W1973371295 @default.
- W4319265493 cites W1975389666 @default.
- W4319265493 cites W1976019213 @default.
- W4319265493 cites W1977514547 @default.
- W4319265493 cites W1987332330 @default.
- W4319265493 cites W1990218919 @default.
- W4319265493 cites W1992203578 @default.
- W4319265493 cites W1992595542 @default.
- W4319265493 cites W1995360097 @default.
- W4319265493 cites W1995549311 @default.
- W4319265493 cites W1995778321 @default.
- W4319265493 cites W1997128521 @default.
- W4319265493 cites W1998189511 @default.
- W4319265493 cites W2007760226 @default.
- W4319265493 cites W2010246713 @default.
- W4319265493 cites W2010394656 @default.
- W4319265493 cites W2011094102 @default.
- W4319265493 cites W2011320047 @default.
- W4319265493 cites W2012848446 @default.
- W4319265493 cites W2015480153 @default.
- W4319265493 cites W2018181455 @default.
- W4319265493 cites W2023962370 @default.
- W4319265493 cites W2025797408 @default.
- W4319265493 cites W2025976140 @default.
- W4319265493 cites W2027848563 @default.
- W4319265493 cites W2036802268 @default.
- W4319265493 cites W2040073285 @default.
- W4319265493 cites W2042393535 @default.
- W4319265493 cites W2043292527 @default.
- W4319265493 cites W2044842134 @default.
- W4319265493 cites W2046835548 @default.
- W4319265493 cites W2048581072 @default.
- W4319265493 cites W2051263030 @default.
- W4319265493 cites W2060400255 @default.
- W4319265493 cites W2060969944 @default.
- W4319265493 cites W2061833498 @default.
- W4319265493 cites W2062990061 @default.
- W4319265493 cites W2065341809 @default.
- W4319265493 cites W2065357486 @default.
- W4319265493 cites W2065738753 @default.
- W4319265493 cites W2067147530 @default.
- W4319265493 cites W2072652550 @default.
- W4319265493 cites W2074016659 @default.
- W4319265493 cites W2074570091 @default.
- W4319265493 cites W2077374589 @default.
- W4319265493 cites W2079722382 @default.
- W4319265493 cites W2084913591 @default.
- W4319265493 cites W2089880505 @default.
- W4319265493 cites W2095447564 @default.
- W4319265493 cites W2096193724 @default.
- W4319265493 cites W2097225903 @default.
- W4319265493 cites W2102092558 @default.
- W4319265493 cites W2102773298 @default.
- W4319265493 cites W2104221788 @default.
- W4319265493 cites W2106375468 @default.
- W4319265493 cites W2109242838 @default.
- W4319265493 cites W2111304405 @default.
- W4319265493 cites W2113758182 @default.
- W4319265493 cites W2117561082 @default.
- W4319265493 cites W2117787632 @default.
- W4319265493 cites W2121090336 @default.
- W4319265493 cites W2121379737 @default.
- W4319265493 cites W2123649031 @default.
- W4319265493 cites W2128508619 @default.
- W4319265493 cites W2132297623 @default.
- W4319265493 cites W2132980997 @default.
- W4319265493 cites W2140549509 @default.
- W4319265493 cites W2140986639 @default.