A number of studies have reported the involvement of the ventral hippocampus (vHip) and the lateral septum (LS) in negative emotional responses. Besides these well‐documented functions, they are also thought to control feeding behavior. In particular, optogenetic and pharmacogenetic interventions to LS‐projecting vHip neurons have demonstrated that the vHip^→LS neural circuit exerts an inhibition on feeding behavior. However, there have been no reports of vHip neuronal activity during feeding. Here, we focused on LS‐projecting vCA1 neurons (vCA1^→LS) and monitored their activity during feeding behaviors in mice. vCA1^→LS neurons were retrogradely labeled with adeno‐associated virus carrying a ratiometric Ca²⁺ indicator and measured compound Ca²⁺ dynamics by fiber photometry. We first examined vCA1^→LS activity in random food‐exploring behavior and found that vCA1^→LS activation seemed to coincide with food intake; however, our ability to visually confirm this during freely moving behaviors was not sufficiently reliable. We next examined vCA1^→LS activity in a goal‐directed, food‐seeking lever‐press task which temporally divided the mouse state into preparatory, effort, and consummatory phases. We observed vCA1^→LS activation in the postprandial period during the consummatory phase. Such timing‐ and pathway‐specific activation was not observed from pan‐vCA1 neurons. In contrast, reward omission eliminated this activity, indicating that vCA1^→LS activation is contingent on the food reward. Sated mice pressed the lever significantly fewer times but still ate food; however, vCA1^→LS neurons were not activated, suggesting that vCA1^→LS neurons did not respond to habitual behavior. Combined, these results suggest that gastrointestinal interoception rather than food‐intake motions or external sensations are likely to coincide with vCA1^→LS activity. Accordingly, we propose that vCA1^→LS neurons discriminate between matched or unmatched predictive bodily states in which incoming food will satisfy an appetite. We also demonstrate that vCA1^→LS neurons are activated in aversive/anxious situations in an elevated plus maze and tail suspension test. Future behavioral tests utilizing anxious conflict and food intake may reconcile the multiple functions of vCA1^→LS neurons.

中文翻译：

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喂养过程中突出到侧隔的腹侧 CA1 海马神经元的激活

许多研究报告了腹侧海马（vHip）和侧隔（LS）参与负面情绪反应。除了这些有据可查的功能外，它们还被认为可以控制进食行为。特别是，对 LS 投射 vHip 神经元的光遗传学和药物遗传学干预表明，vHip ^{→ LS}神经回路对摄食行为具有抑制作用。然而，没有关于喂养期间 vHip 神经元活动的报道。在这里，我们专注于 LS 投射的 vCA1 神经元（vCA1 ^→LS），并监测它们在小鼠进食行为期间的活动。vCA1 ^→LS神经元被携带比例 Ca ^{2+的腺相关病毒逆行标记}指示剂和通过纤维光度法测量的化合物Ca ²⁺动力学。我们首先检查了随机食物探索行为中的 vCA1 ^→LS活性，发现 vCA1 ^→LS激活似乎与食物摄入一致；然而，我们在自由移动行为中目视确认这一点的能力不够可靠。接下来，我们在目标导向、寻求食物的杠杆按压任务中检查了 vCA1 ^{→LS活动，该任务将鼠标状态时间划分为准备、努力和完成阶段。}我们观察到 vCA1 ^→LS在完成阶段的餐后阶段激活。pan-vCA1 神经元没有观察到这种时间和通路特异性的激活。相比之下，奖励遗漏消除了这种活动，表明 vCA1 ^→LS激活取决于食物奖励。饱食的老鼠按下杠杆的次数明显减少，但仍然吃东西；然而，vCA1 ^→LS神经元没有被激活，这表明 vCA1 ^→LS神经元对习惯性行为没有反应。综合起来，这些结果表明胃肠内感受而不是食物摄入运动或外部感觉可能与 vCA1 ^{→ LS}活动一致。因此，我们建议 vCA1 ^→LS神经元区分匹配或不匹配的预测身体状态，在这种状态下，传入的食物将满足食欲。我们还证明了 vCA1 ^→LS神经元在高架十字迷宫和悬尾测试中的厌恶/焦虑情况下被激活。未来利用焦虑冲突和食物摄入的行为测试可能会调和 vCA1 ^→LS神经元的多种功能。