Departamento de Psicobiologia, Universidade Federal de São Paulo - UNIFESP, São Paulo 04023-062, Brazil.
Departamento de Psicobiologia, Universidade Federal de São Paulo - UNIFESP, São Paulo 04023-062, Brazil; Departamento de Psicologia, Universidade Ibirapuera - UNIB, São Paulo 04661-100, Brazil.
Neurobiol Learn Mem. 2020 May;171:107216. doi: 10.1016/j.nlm.2020.107216. Epub 2020 Mar 20.
Although stimuli that are associated often overlap in time, previous events can also predict the occurrence of a later aversive stimulus and be associated with it to better guide future behavior. Associations of stimuli separated in time have been studied using discrete stimulus as the conditioned stimulus (CS) in trace conditioning or, more recently in our lab, using the context as the CS in contextual fear conditioning with temporal discontinuity (CFC-5s), a task that simultaneously includes the processing of time and space components. It is thought that fear memories are encoded by the strengthening of synaptic connections in a distributed neural network. However, it is unclear how this temporal factor, which may differentially require the maintenance of the stimulus over time, affects the interactivity between brain regions to form the association. Because the prelimbic cortex (PL) and the hippocampus have been individually engaged in trace conditioning, they may functionally interact to encode associations separated in time. This is anatomically supported by direct ipsilateral projections from the ventral hippocampal CA1 region (vCA1) to PL. The aim of the present study was to investigate the effect of the functional disconnection of vCA1 and PL on CFC-5s using pre-training asymmetric reversible inactivation with muscimol. For comparison, we also observed its effect on contextual fear conditioning (CFC). Results showed that the functional disconnection impaired the encoding of the CFC-5s, an association of stimuli separated in time, while did not affect the CFC, an association of stimuli overlapped in time. In addition, the preserved connection in one hemisphere was sufficient to support the encoding of CFC-5s. The time interval by itself did not increase freezing responses and both CFC and CFC tasks had similar generalization and higher freezing responses than unconditioned groups. These findings suggest that the time factor alters the requirement of the interactivity of the brain regions underlying fear conditioning and extend the relevance of hippocampal-prefrontal interactions in memory.
尽管经常重叠的刺激物在时间上相关，但先前的事件也可以预测随后厌恶刺激物的发生，并与之相关联，以更好地指导未来的行为。已经使用离散刺激物作为条件刺激 (CS) 在痕迹条件反射中研究了时间上分离的刺激物的关联，或者最近在我们的实验室中，使用上下文作为条件刺激 (CS) 在具有时间不连续性的上下文恐惧条件反射 (CFC-5s) 中，同时包括时间和空间成分的处理。人们认为恐惧记忆是通过在分布式神经网络中加强突触连接来编码的。然而，目前尚不清楚这个时间因素（可能需要随着时间的推移不同地维持刺激）如何影响大脑区域之间的相互作用以形成关联。由于边缘前皮质 (PL) 和海马体分别参与了痕迹条件反射，因此它们可能通过来自海马体 CA1 腹侧区 (vCA1) 的直接同侧投射来进行功能交互，以编码时间上分离的关联。本研究的目的是使用预先训练的不对称可逆失活来研究 vCA1 和 PL 的功能分离对 CFC-5s 的影响，使用 muscimol。为了进行比较，我们还观察了其对上下文恐惧条件反射 (CFC) 的影响。结果表明，功能分离会损害时间上分离的刺激物关联的 CFC-5s 的编码，而不会影响时间上重叠的刺激物关联的 CFC。此外，一个半球中保留的连接足以支持 CFC-5s 的编码。时间间隔本身不会增加冻结反应，CFC 和 CFC 任务都具有相似的泛化和比未条件组更高的冻结反应。这些发现表明，时间因素改变了恐惧条件反射中大脑区域相互作用的要求，并扩展了海马体-前额叶相互作用在记忆中的相关性。
