Departamento de Psicobiologia, Universidade Federal de São Paulo - UNIFESP, São Paulo, 04023-062, Brazil.
Universidade Cruzeiro do Sul - UNICSUL, São Paulo, 08060-070, Brazil.
Sci Rep. 2023 Aug 11;13(1):13087. doi: 10.1038/s41598-023-39946-1.
In fear conditioning with time intervals between the conditioned (CS) and unconditioned (US) stimuli, a neural representation of the CS must be maintained over time to be associated with the later US. Usually, temporal associations are studied by investigating individual brain regions. It remains unknown, however, the effect of the interval at the network level, uncovering functional connections cooperating for the CS transient memory and its fear association. We investigated the functional network supporting temporal associations using a task in which a 5-s interval separates the contextual CS from the US (CFC-5s). We quantified c-Fos expression in forty-nine brain regions of male rats following the CFC-5s training, used c-Fos correlations to generate functional networks, and analyzed them by graph theory. Control groups were trained in contextual fear conditioning, in which CS and US overlap. The CFC-5s training additionally activated subdivisions of the basolateral, lateral, and medial amygdala; prelimbic, infralimbic, perirhinal, postrhinal, and intermediate entorhinal cortices; ventral CA1 and subiculum. The CFC-5s network had increased amygdala centrality and higher amygdala internal and external connectivity with the retrosplenial cortex, thalamus, and hippocampus. Amygdala and thalamic nuclei were network hubs. Functional connectivity among these brain regions could support CS transient memories and their association.
在条件刺激(CS)和非条件刺激(US)之间有时间间隔的恐惧条件反射中,CS 的神经表示必须随时间维持以与随后的 US 相关联。通常,通过研究单个脑区来研究时间关联。然而,在网络水平上的间隔的影响尚不清楚,揭示了合作进行 CS 瞬态记忆及其恐惧关联的功能连接。我们使用间隔为 5 秒的上下文 CS 与 US (CFC-5s)的任务来研究支持时间关联的功能网络。我们在 CFC-5s 训练后量化了雄性大鼠 49 个脑区的 c-Fos 表达,使用 c-Fos 相关性生成功能网络,并通过图论进行分析。对照组在上下文恐惧条件反射中进行训练,其中 CS 和 US 重叠。CFC-5s 训练还激活了外侧、中间和内侧杏仁核的亚区;前额叶皮层、下边缘皮层、旁嗅皮层、后嗅皮层和中间内嗅皮层;腹侧 CA1 和下托。CFC-5s 网络增加了杏仁核的中心性,以及杏仁核与后扣带回皮层、丘脑和海马体的内部和外部连接性更高。杏仁核和丘脑核是网络枢纽。这些脑区之间的功能连接可以支持 CS 瞬态记忆及其关联。