目标:环境背景,可靠地预测食物供应,可以在相同的环境背景下增加食欲。然而,饥饿是发展这种环境诱导喂养(CIF)反应所必需的,这表明对饥饿敏感的神经回路将内部能量状态与特定环境联系起来。由于Agouti相关肽(AgRP)神经元被能量不足激活,我们假设AgRP神经元对驱动CIF既必要又足够。
方法:为了检查AgRP神经元在CIF过程中的作用,我们使用GCaMP7f的光纤测光法,AgRP神经元的化学激活,以及光遗传学控制AgRP神经元以促进化学遗传学不允许的急性时间控制。
结果:仅在上下文训练期间禁食时观察到测试时的ACIF反应,并且测试时的AgRP种群活动显示出对食物的抑制反应减弱,提示增加的食物寻求和/或减少的饱腹感信号驱动增加的进食反应在测试.有趣的是,上下文训练期间AgRP神经元的化学遗传激活没有增加CIF,可能需要精确的时间点火特性。的确,在上下文训练期间终止AgRP神经元光刺激(上下文中的ON-OFF),在有或没有食物的情况下,增加的CIF.此外,在没有食物供应的情况下,在禁食小鼠的上下文训练期间,AgRP神经元的光抑制足以驱动后续CIF.
结论:我们的结果表明,当AgRP活性的急性抑制在时间上与环境暴露相匹配时,AgRP神经元调节CIF的获得。这些结果将急性AgRP抑制确立为突出的神经事件,强调了饥饿对联想学习的影响。
OBJECTIVE: An environmental context, which reliably predicts food availability, can increase the appetitive food drive within the same environment context. However, hunger is required for the development of such a context-induced feeding (CIF) response, suggesting the neural circuits sensitive to hunger link an internal energy state with a particular environment context. Since Agouti related peptide (AgRP) neurons are activated by energy deficit, we hypothesised that AgRP neurons are both necessary and sufficient to drive CIF.
METHODS: To examine the role of AgRP neurons in the CIF process, we used fibre photometry with GCaMP7f, chemogenetic activation of AgRP neurons, as well as optogenetic control of AgRP neurons to facilitate acute temporal control not permitted with chemogenetics.
RESULTS: A CIF response at test was only observed when mice were fasted during context training and AgRP population activity at test showed an attenuated inhibitory response to food, suggesting increased food-seeking and/or decreased satiety signalling drives the increased feeding response at test. Intriguingly, chemogenetic activation of AgRP neurons during context training did not increase CIF, suggesting precise temporal firing properties may be required. Indeed, termination of AgRP neuronal photostimulation during context training (ON-OFF in context), in the presence or absence of food, increased CIF. Moreover, photoinhibition of AgRP neurons during context training in fasted mice was sufficient to drive a subsequent CIF in the absence of food.
CONCLUSIONS: Our results suggest that AgRP neurons regulate the acquisition of CIF when the acute inhibition of AgRP activity is temporally matched to context exposure. These results establish acute AgRP inhibition as a salient neural event underscoring the effect of hunger on associative learning.