Research involving human participants indicates that memories of recently eaten meals limit how much is eaten during subsequent eating episodes; yet, the brain regions that mediate the inhibitory effects of ingestion-related memory on future intake are largely unknown. We hypothesize that dorsal hippocampal (dHC) neurons, which are critical for episodic memories of personal experiences, mediate the inhibitory effects of ingestion-related memory on future intake. Our research program aimed at testing this hypothesis has been influenced in large part by our mentor James McGaugh and his research on posttraining manipulations. In the present study, we used an activity-guided optogenetic approach to test the prediction that if dHC glutamatergic neurons limit future intake through a process that requires memory consolidation, then inhibition should increase subsequent intake when given soon after the end of a meal but delayed inhibition should have no effect. Viral vectors containing CaMKIIα-eArchT3.0-eYFP and fiber optic probes were placed in the dHC of male Sprague-Dawley rats. Compared to intake on a day when no inhibition was given, postmeal inhibition of dHC glutamatergic neurons given for 10 min after the end of a saccharin meal increased the likelihood that rats would consume a second meal 90 min later and significantly increased the amount of saccharin solution consumed during that next meal when the neurons were no longer inhibited. Importantly, delayed inhibition given 80 min after the end of the saccharin meal did not affect subsequent intake of saccharin. Given that saccharin has minimal postingestive gastric consequences, these effects are not likely due to the timing of interoceptive visceral cues generated by the meal. These data show that dHC glutamatergic neural activity is necessary during the early postprandial period for limiting future intake and suggest that these neurons inhibit future intake by consolidating the memory of the preceding meal.

涉及人类参与者的研究表明，最近吃过的饭菜的记忆限制了在随后的进食事件中吃多少；然而，调节摄入相关记忆对未来摄入量的抑制作用的大脑区域在很大程度上是未知的。我们假设对个人经历的情景记忆至关重要的背侧海马 (dHC) 神经元介导了摄入相关记忆对未来摄入的抑制作用。我们旨在验证这一假设的研究计划在很大程度上受到了我们的导师 James McGaugh 和他对训练后操作的研究的影响。在本研究中，我们使用活动引导的光遗传学方法来测试预测，如果 dHC 谷氨酸能神经元通过需要记忆巩固的过程限制未来摄入，那么在饭后不久给予抑制应该会增加随后的摄入量，但延迟抑制应该没有效果。将含有 CaMKIIα-eArchT3.0-eYFP 和光纤探针的病毒载体置于雄性 Sprague-Dawley 大鼠的 dHC 中。与未给予抑制的当天摄入相比，在糖精餐结束后 10 分钟给予 dHC 谷氨酸能神经元的餐后抑制增加了大鼠在 90 分钟后进食第二餐的可能性，并显着增加了糖精溶液的量当神经元不再受到抑制时，在下一餐中消耗。重要的是，在糖精餐结束后 80 分钟给予延迟抑制不会影响随后的糖精摄入。鉴于糖精对胃后遗症的影响很小，这些影响不太可能是由于膳食产生的内感受内脏暗示的时间。这些数据表明，在餐后早期，dHC 谷氨酸能神经活动对于限制未来摄入是必要的，并表明这些神经元通过巩固前一餐的记忆来抑制未来的摄入。