Social experience dependent modification of gene regulation and circuit function

摘要： 动物通过社会经验来调整自己的行为，以增加身体健康。分子和神经 依赖社会经验的行为调节背后的基于回路的机制仍然不清楚。 新出现的证据表明，感觉体验、染色质和行为之间存在密切联系 修改。染色质调节缺陷与许多神经精神障碍有关。 要了解染色质在调节行为中的作用，需要具有已识别的基因和 神经回路与刻板印象行为有明确的因果联系。黑腹果蝇是一种极好的 这个模型很好地解释了求爱行为中的这些联系。在黑腹果蝇中，无果(Fru)和 双性(Dsx)是控制先天和后天特定性别求偶的转录调控主控。 行为分别为。FRU在2000个相互连接的神经元中表达，这些神经元标记着求爱回路。社交 与世隔绝的野生型雄性比群居的雄性表现出更高的求偶能力。相反，社交孤立的兄弟 然而，突变的雄性不会求爱，如果组合在一起，他们会利用嗅觉来学习向男性或女性求爱。这 学习需要dsx基因，该基因在求爱回路的决策神经元中与fru共同表达。 社会经验如何调节FEU和Dsx在求爱回路中的表达以改变回路功能仍未有定论 未知。在已发表的和初步的数据中，我们证明了社会经验和信息素信号 在外周和中枢求爱中诱导基于染色质的FRU和DSX表达的重编程 电路。我们还发现，社交线索改变了外周目标神经调节基因的表达 神经元，它改变神经元的敏感性和电路功能。我们假设对社交信号的检测 在中央大脑中，染色质围绕着行为开关基因如Fru和Dsx重新编程，这 进而调节电路功能和行为。为了测试这一点，我们建议确定社会经验和 Fru和dsx基因周围染色质的信息素信号依赖性变化及其对下游的影响 靶基因表达、电路功能和行为输出。

SUMMARY: Animals modulate their behaviors with social experience to increase fitness. The molecular and neural circuit-based mechanisms underlying social experience-dependent behavioral modulation remains unclear. Emerging evidence indicates the intimate connection among sensory experience, chromatin and behavioral modifications. Defects in chromatin modulation are associated with many neuropsychiatric disorders. Understanding the role of chromatin in regulating behaviors requires model systems with identified genes and neural circuits with clear causal links to stereotyped behaviors. The Drosophila melanogaster is an excellent model where these links were well elucidated for courtship behaviors. In D. melanogaster, Fruitless (Fru) and Doublesex (Dsx) are master transcriptional regulators that control innate and learned sex-specific courtship behaviors, respectively. fru is expressed in 2000 interconnected neurons marking courtship circuits. Socially isolated wild type males show elevated courtship compared to grouped males. Conversely, socially isolated fruM mutant males do not court, however, if grouped, they use olfaction to learn to court either males or females. This learning requires the gene dsx, which is co-expressed with fru in decision-making neurons of courtship circuits. How social experience regulates fru and dsx expression in the courtship circuits to modify circuit function remains unknown. In published and preliminary data, we demonstrated that social experience and pheromone signaling induces chromatin-based reprogramming of fru and dsx expression in the peripheral and central courtship circuits. We also found that social cues change Fru target neuromodulatory gene expression in the peripheral neurons, which alter neuronal sensitivity and circuit function. We hypothesize that detection of social signals reprograms chromatin around behavioral switch genes such as Fru and Dsx in the central brain, which in turn modulate circuit function and behaviors. To test this, we propose to identify social experience and pheromone signaling-dependent changes in chromatin around fru and dsx genes, their effects on downstream target gene expression, circuit function and behavioral outputs.