Department of Neuroscience, Psychology, Drug Research and Child Health, Pharmacology and Toxicology Unit, University of Florence, Florence, Italy.
INRAE, Bordeaux INP, Nutrition and Integrative Neurobiology, UMR 1286, University of Bordeaux, 33077, Bordeaux, France.
Sci Rep. 2024 May 17;14(1):11283. doi: 10.1038/s41598-024-61998-0.
Several lines of evidence demonstrate that the brain histaminergic system is fundamental for cognitive processes and the expression of memories. Here, we investigated the effect of acute silencing or activation of histaminergic neurons in the hypothalamic tuberomamillary nucleus (TMN neurons) in vivo in both sexes in an attempt to provide direct and causal evidence of the necessary role of these neurons in recognition memory formation and retrieval. To this end, we compared the performance of mice in two non-aversive and non-rewarded memory tests, the social and object recognition memory tasks, which are known to recruit different brain circuitries. To directly establish the impact of inactivation or activation of TMN neurons, we examined the effect of specific chemogenetic manipulations during the formation (acquisition/consolidation) or retrieval of recognition memories. We consistently found that acute chemogenetic silencing of TMN neurons disrupts the formation or retrieval of both social and object recognition memory in males and females. Conversely, acute chemogenetic activation of TMN neurons during training or retrieval extended social memory in both sexes and object memory in a sex-specific fashion. These results suggest that the formation or retrieval of recognition memory requires the tonic activity of histaminergic neurons and strengthen the concept that boosting the brain histaminergic system can promote the retrieval of apparently lost memories.
有几条证据表明，脑内组胺能系统对于认知过程和记忆的表达至关重要。在这里，我们研究了在体内急性沉默或激活下丘脑结节乳头核（TMN 神经元）中的组胺能神经元对雄性和雌性动物的识别记忆形成和检索的影响，试图提供这些神经元在识别记忆形成和检索中的必要作用的直接和因果证据。为此，我们比较了小鼠在两种非厌恶和无奖励的记忆测试中的表现，即社交和物体识别记忆任务，这两种任务已知会招募不同的脑回路。为了直接确定 TMN 神经元的失活或激活的影响，我们在识别记忆的形成（获得/巩固）或检索过程中检查了特定化学遗传操作的效果。我们一致发现，TMN 神经元的急性化学遗传沉默会破坏雄性和雌性动物的社交和物体识别记忆的形成或检索。相反，在训练或检索期间，TMN 神经元的急性化学遗传激活会延长两性的社交记忆，并以性别特异性的方式延长物体记忆。这些结果表明，识别记忆的形成或检索需要组胺能神经元的紧张活动，并加强了这样一种概念，即增强大脑组胺能系统可以促进明显丢失的记忆的检索。
