Regulation of actions and habits by ventral hippocampal trkB and adolescent corticosteroid exposure.
Regulation of actions and habits by ventral hippocampal trkB and adolescent corticosteroid exposure.
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DOI：
10.1371/journal.pbio.2003000
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发表时间：
2017-11
期刊：
影响因子：
9.8
通讯作者：
Gourley SL
中科院分区：
文献类型：
--
作者：
Barfield ET;Gerber KJ;Zimmermann KS;Ressler KJ;Parsons RG;Gourley SL
In humans and rodents, stress promotes habit-based behaviors that can interfere with action–outcome decision-making. Further, developmental stressor exposure confers long-term habit biases across rodent–primate species. Despite these homologies, mechanisms remain unclear. We first report that exposure to the primary glucocorticoid corticosterone (CORT) in adolescent mice recapitulates multiple neurobehavioral consequences of stressor exposure, including long-lasting biases towards habit-based responding in a food-reinforced operant conditioning task. In both adolescents and adults, CORT also caused a shift in the balance between full-length tyrosine kinase receptor B (trkB) and a truncated form of this neurotrophin receptor, favoring the inactive form throughout multiple corticolimbic brain regions. In adolescents, phosphorylation of the trkB substrate extracellular signal-regulated kinase 42/44 (ERK42/44) in the ventral hippocampus was also diminished, a long-term effect that persisted for at least 12 wk. Administration of the trkB agonist 7,8-dihydroxyflavone (7,8-DHF) during adolescence at doses that stimulated ERK42/44 corrected long-lasting corticosterone-induced behavioral abnormalities. Meanwhile, viral-mediated overexpression of truncated trkB in the ventral hippocampus reduced local ERK42/44 phosphorylation and was sufficient to induce habit-based and depression-like behaviors. Together, our findings indicate that ventral hippocampal trkB is essential to goal-directed action selection, countering habit-based behavior otherwise facilitated by developmental stress hormone exposure. They also reveal an early-life sensitive period during which trkB–ERK42/44 tone determines long-term behavioral outcomes. Stress can impair the ability of individuals to select actions based on their consequences, promoting instead the acquisition of habits—automatic behaviors that are insensitive to action–outcome relationships. Stress in adolescence can have particularly long-lasting consequences, affecting behavior and mood regulation even in adulthood. Here, we show that adolescent mice exposed to a stress hormone developed biases towards habits and amotivation (a symptom of depression) in adulthood. We investigated the role of the stress-sensitive tyrosine kinase receptor B (trkB) receptor, a protein that regulates synaptic strength and plasticity in the mammalian nervous system. This receptor was modified by adolescent experience throughout multiple brain regions, but the changes were particularly long lasting in the ventral hippocampus—a brain region involved in mood regulation. Experimentally reducing the activity of the receptor recapitulated the behavioral abnormalities induced by the stress hormone. Meanwhile, pharmacological stimulation of the receptor corrected these abnormalities and had long-lasting antidepressant-like effects that persisted even after drug treatment ended. Thus, pharmacological interventions that augment trkB activity may be particularly efficacious in treating neurobehavioral deficits in adolescents exposed to chronic stress.
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影响因子：
2.7
作者：
Burton, Brian G.;Hok, Vincent;Poucet, Bruno
通讯作者：
Poucet, Bruno
DOI：
10.1080/14640748308400912
发表时间：
1983-01-01
期刊：
QUARTERLY JOURNAL OF EXPERIMENTAL PSYCHOLOGY SECTION B-COMPARATIVE AND PHYSIOLOGICAL PSYCHOLOGY
影响因子：
--
作者：
DICKINSON, A;NICHOLAS, DJ;ADAMS, CD
通讯作者：
ADAMS, CD
影响因子：
3
作者：
Griffiths KR;Morris RW;Balleine BW
通讯作者：
Balleine BW
影响因子：
7.3
作者：
Boltaev, Umed;Meyer, Yves;Sames, Dalibor
通讯作者：
Sames, Dalibor
DOI：
10.1073/pnas.1208342109
发表时间：
2012-12-11
影响因子：
11.1
作者：
Gourley, Shannon L.;Swanson, Andrew M.;Taylor, Jane R.
通讯作者：
Taylor, Jane R.