Wang Qian, Jin Jingji, Maren Stephen
Department of Biology, Texas A&M University, College Station, TX 77843-3474, United States.
Institute for Neuroscience, Texas A&M University, College Station, TX 77843-3474, United States.
Neurobiol Learn Mem. 2016 Oct;134 Pt A(Pt A):38-43. doi: 10.1016/j.nlm.2016.04.002. Epub 2016 Apr 7.
Anatomical disconnection of the ventral hippocampus (VH) and medial prefrontal cortex (mPFC) impairs the renewal of extinguished fear in rats. Here we examined whether subpopulations of neurons in the VH that project to the mPFC, including the prelimbic cortex (PL) and infralimbic cortex (IL), are selectively or differentially engaged by the renewal of fear to an extinguished auditory conditioned stimulus (CS). Rats were ipsilaterally injected with two distinct fluorescent retrograde tracers into the IL and PL and then underwent fear conditioning, extinction and retrieval in distinct contexts. Ventral hippocampal neurons were found to project to both IL and PL, and a small number of neurons projected to both regions. Fos expression was similarly elevated in each subpopulation of mPFC-projecting neuron in animals tested outside the extinction context relative to those tested in the extinction context or home controls. Interestingly, this pattern of results is not consistent with circuit models suggesting a differential role for VH projections to PL and IL in the bidirectional regulation of fear expression after extinction. Rather, these data suggest that projections from the VH to both PL and IL are uniquely involved in fear renewal, but not the suppression of fear after extinction. VH neurons may drive fear renewal by fostering fear expression by exciting PL while limiting fear suppression by inhibiting IL.
腹侧海马体（VH）与内侧前额叶皮质（mPFC）之间的解剖学连接中断会损害大鼠消退恐惧的恢复。在此，我们研究了VH中投射至mPFC的神经元亚群，包括前边缘皮质（PL）和边缘下皮质（IL），是否会因对已消退的听觉条件刺激（CS）的恐惧恢复而被选择性或差异性激活。给大鼠同侧注射两种不同的荧光逆行示踪剂至IL和PL，然后在不同环境中进行恐惧条件反射、消退和恢复测试。发现腹侧海马神经元投射至IL和PL，且有少量神经元投射至这两个区域。相对于在消退环境中测试的动物或在家中作为对照的动物，在消退环境外测试的动物中，投射至mPFC的每个神经元亚群中Fos表达均同样升高。有趣的是，这一结果模式与电路模型不一致，该模型表明VH投射至PL和IL在消退后恐惧表达的双向调节中具有不同作用。相反，这些数据表明，VH至PL和IL的投射独特地参与了恐惧恢复，但不参与消退后恐惧的抑制。VH神经元可能通过兴奋PL促进恐惧表达同时抑制IL限制恐惧抑制来驱动恐惧恢复。
