Department of Biomedical Sciences, Marquette University, Milwaukee, WI 53233, USA.
Department of Biomedical Sciences, Marquette University, Milwaukee, WI 53233, USA.
Neurobiol Learn Mem. 2022 Apr;190:107610. doi: 10.1016/j.nlm.2022.107610. Epub 2022 Mar 14.
The hippocampus is crucial for associative fear learning when the anticipation of threat requires temporal or contextual binding of predictive stimuli as in trace and contextual fear conditioning. Compared with the dorsal hippocampus, far less is known about the contribution of the ventral hippocampus to fear learning. The ventral hippocampus, which is highly interconnected with defensive and emotional networks, has a prominent role in both innate and learned affective behaviors including anxiety, fear, and reward. Lesions or temporary inactivation of the ventral hippocampus impair both cued and contextual fear learning, but whether the ventral hippocampal role in learning is driven by affective processing, associative encoding, or both is not clear. Here, we used trace fear conditioning in mixed sex cohorts to assess the contribution of shock-encoding to the acquisition of cued and contextual fear memories. Trace conditioning requires subjects to associate an auditory conditional stimulus (CS) with a shock unconditional stimulus (UCS) that are separated in time by a 20-s trace interval. We first recorded neuronal activity in the ventral hippocampus during trace fear conditioning and found that ventral CA1 predominantly encoded the shock reinforcer. Potentiated firing to the CS was evident at testing, but no encoding of the trace interval was observed. We then tested the necessity of shock encoding for conditional fear acquisition by optogenetically silencing ventral hippocampal activity during the UCS on each trial of training. Contrary to our predictions, preventing hippocampal shock-evoked firing did not impair associative fear. Instead, it led to a more prolonged expression of CS freezing across test trials, an effect observed in males, but not females. Contextual fear learning was largely intact, although a subset of animals in each sex were differentially affected by shock-silencing. Taken together, the results show that shock encoding in the ventral hippocampus modulates the expression of learned fear in a sex-specific manner.
海马体对于联想性恐惧学习至关重要，当对威胁的预期需要预测性刺激的时间或上下文绑定时，例如在痕迹和情境恐惧条件作用中。与背侧海马体相比，人们对腹侧海马体在恐惧学习中的贡献知之甚少。腹侧海马体与防御和情绪网络高度连接，在包括焦虑、恐惧和奖励在内的先天和习得的情感行为中具有突出作用。腹侧海马体的损伤或暂时失活会损害线索和情境恐惧学习，但腹侧海马体在学习中的作用是由情感处理、联想编码还是两者共同驱动尚不清楚。在这里，我们使用痕迹恐惧条件作用在混合性别队列中评估了对学习的影响。痕迹条件作用要求受试者将听觉条件刺激 (CS) 与在时间上相隔 20 秒的声音无条件刺激 (UCS) 相关联。我们首先在痕迹恐惧条件作用期间记录腹侧海马体中的神经元活动，发现腹侧 CA1 主要编码了电击强化物。在测试时，CS 的增强放电是明显的，但没有观察到痕迹间隔的编码。然后，我们通过在每个训练试验的 UCS 期间用光遗传学沉默腹侧海马体活动来测试条件恐惧获得所需的电击编码的必要性。与我们的预测相反，阻止海马体电击诱发的放电并没有损害联想性恐惧。相反，它导致了 CS 冻结在测试试验中的更长时间表达，这种效应在雄性中观察到，但在雌性中没有观察到。情境恐惧学习基本完整，尽管每个性别中的一组动物受到电击沉默的影响不同。总之，这些结果表明，腹侧海马体中的电击编码以性别特异性的方式调节习得性恐惧的表达。
