近日，美国埃默里大学和佐治亚理工学院教授Annabelle C. Singer及其小组发现了目标特异性海马抑制门学习。该项研究成果发表在2025年4月9日出版的《自然》上。

本研究表明，小鼠海马CA3中小白蛋白（PV）阳性的中间神经元在识别和开发新的食物位置方面具有诱导作用，从而降低目标周围的抑制活性，从而使再激活将目标位置与食物结果结合起来。当缺乏食物的小鼠学习寻找食物时，CA3中的PV中间神经元大大减少了接近目标位置和目标位置的放电。当老鼠学习时，这种抑制会减少预期的奖励位置，并且在正确的试验中更加突出。

稀疏光遗传刺激防止目标相关的PV中间神经元放电损伤目标位置的学习。破坏与目标相关的PV中间神经元活动减少，会在获得食物后损害新目标位置的重新激活，这一过程将先前的位置与食物结果联系起来，这样小鼠就知道以后去哪里寻找食物。这些结果表明，目标选择性和目标预测性抑制活动的减少使关键位置的学习、表征和结果关联成为可能。

据了解，新环境中的目标导向导航需要快速识别和利用重要位置。确定新的目标位置依赖于快速表示位置并将位置信息与关键结果（如食物）联系起来的神经计算。然而，在行为相关位置触发这些计算的机制尚不清楚。

附：英文原文

Title: Goal-specific hippocampal inhibition gates learning

Author: Jeong, Nuri, Zheng, Xiao, Paulson, Abigail L., Prince, Stephanie M., Nguyen, Victor P., Thomas, Sherina R., Gilpin, Caroline E., Goodson, Matthew C., Singer, Annabelle C.

Issue&Volume: 2025-04-09

Abstract: Goal-directed navigation in a new environment requires quickly identifying and exploiting important locations. Identifying new goal locations depends on neural computations that rapidly represent locations and connect location information to key outcomes such as food1. However, the mechanisms to trigger these computations at behaviourally relevant locations are not well understood. Here we show that parvalbumin (PV)-positive interneurons in the mouse hippocampal CA3 have a causal role in identifying and exploiting new food locations such that decreases in inhibitory activity around goals enable reactivation to bind goal locations to food outcomes. PV interneurons in the CA3 substantially reduce firing on approach to and at goal locations while food-deprived mice learn to find food. These inhibitory decreases anticipate reward locations as the mice learn and are more prominent on correct trials. Sparse optogenetic stimulation to prevent goal-related decreases in PV interneuron firing impaired learning of goal locations. Disrupting goal-related decreases in PV interneuron activity impaired the reactivation of new goal locations after receipt of food, a process that associates previous locations to food outcomes such that the mice know where to seek food later. These results reveal that goal-selective and goal-predictive decreases in inhibitory activity enable learning, representations and outcome associations of crucial locations.

DOI: 10.1038/s41586-025-08868-5

Source: https://www.nature.com/articles/s41586-025-08868-5