Ramirez-Mejia Gerardo, Gil-Lievana Elvi, Urrego-Morales Oscar, Galvez-Marquez Donovan, Hernández-Ortiz Eduardo, Carrillo-Lorenzo José Alberto, Bermúdez-Rattoni Federico
División de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, 04510, Mexico City, Mexico.
División de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, 04510, Mexico City, Mexico.
Neuropharmacology. 2023 May 1;228:109464. doi: 10.1016/j.neuropharm.2023.109464. Epub 2023 Feb 15.
Previous studies have shown that dopaminergic activity modulates the salience of novel stimuli enabling the formation of recognition memories. In this work, we hypothesize that dopamine released into the insular cortex (IC) from the ventral tegmental area (VTA) inputs enables the acquisition to consolidate object recognition memory. It has been reported that short training produces weak recognition memories; on the contrary, longer training produces lasting and robust recognition memories. Using a Cre-recombinase under the tyrosine hydroxylase (TH+) promoter mouse model, we photostimulated the VTA-IC dopaminergic pathway during short training or photoinhibited the same pathway during long training while mice explored objects. Our results showed that the photostimulation of the VTA-IC pathway during a short training enables the acquisition of recognition memory. Conversely, photoinhibition of the same pathway during a long training prevents the acquisition of recognition memory. Interestingly, the exploration time of the objects under photoinhibition or photostimulation of the dopaminergic VTA-IC pathway was not altered. Significantly, this enhancement of acquisition of the object recognition memory through the photostimulation of the VTA dopaminergic neurons could be impaired by the blockage of the D1-like receptors into the IC, either before or after the photostimulation. Altogether, our results suggest that dopamine released by the VTA is required during the acquisition to consolidate the object recognition memory through D1-like receptors into the IC without affecting the activity or the motivation to explore objects.
先前的研究表明，多巴胺能活动调节新异刺激的显著性，从而促进识别记忆的形成。在本研究中，我们假设从腹侧被盖区（VTA）输入到岛叶皮质（IC）释放的多巴胺能使物体识别记忆在获取过程中得以巩固。据报道，短时间训练产生的识别记忆较弱；相反，长时间训练产生的识别记忆持久且稳固。我们使用在酪氨酸羟化酶（TH+）启动子下的Cre重组酶小鼠模型，在小鼠探索物体时，在短时间训练期间对VTA-IC多巴胺能通路进行光刺激，或在长时间训练期间对同一通路进行光抑制。我们的结果表明，在短时间训练期间对VTA-IC通路进行光刺激能使小鼠获得识别记忆。相反，在长时间训练期间对同一通路进行光抑制则会阻止小鼠获得识别记忆。有趣的是，在多巴胺能VTA-IC通路光抑制或光刺激下，小鼠对物体的探索时间并未改变。值得注意的是，在光刺激之前或之后，向IC内阻断D1样受体可能会损害通过光刺激VTA多巴胺能神经元而增强的物体识别记忆的获得。总之，我们的结果表明，在获取过程中，VTA释放的多巴胺需要通过D1样受体进入IC，以巩固物体识别记忆，而不影响探索物体的活动或动机。
