Reversing anterior insular cortex neuronal hypoexcitability attenuates compulsive behavior in adolescent rats.

Reversing anterior insular cortex neuronal hypoexcitability attenuates compulsive behavior in adolescent rats.
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DOI:
10.1073/pnas.2121247119
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发表时间:
2022-05-24
影响因子:
11.1
通讯作者:
--
中科院分区:
综合性期刊1区
文献类型:
--
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Clinical evidence suggests that adolescents engage in dangerous activities despite understanding the risks involved, questioning the theory of decreased top-down control of the immature prefrontal cortex promoting adolescent disinhibited behaviors. In the present study, we report that adolescent rats show a much higher degree of inflexible behavior when making decisions under conflict compared to adults. Unexpectedly, we identified a lower excitability of layer 5 pyramidal neurons in the anterior insular cortex (AIC) of adolescent rats and smaller synaptic glutamatergic inputs to these cells but no difference in layer 5 prefrontal cortex pyramidal neurons. Chemogenetic activation of AIC neurons reduced persistent reward-seeking despite punishment, suggesting that the delayed maturation of the insula may promote inflexible reward-related behaviors in adolescent rats. Development of self-regulatory competencies during adolescence is partially dependent on normative brain maturation. Here, we report that adolescent rats as compared to adults exhibit impulsive and compulsive-like behavioral traits, the latter being associated with lower expression of mRNA levels of the immediate early gene zif268 in the anterior insula cortex (AIC). This suggests that underdeveloped AIC function in adolescent rats could contribute to an immature pattern of interoceptive cue integration in decision making and a compulsive phenotype. In support of this, we report that layer 5 pyramidal neurons in the adolescent rat AIC are hypoexcitable and receive fewer glutamatergic synaptic inputs compared to adults. Chemogenetic activation of the AIC attenuated compulsive traits in adolescent rats supporting the idea that in early stages of AIC maturity there exists a suboptimal integration of sensory and cognitive information that contributes to inflexible behaviors in specific conditions of reward availability.
DOI: 10.1073/pnas.0402680101
发表时间: 2004-05-25
影响因子: 11.1
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Gogtay, N;Giedd, JN;Thompson, PM
通讯作者: Thompson, PM
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