Almada R C, Coimbra N C, Brandão M L
Laboratory of Neuroanatomy and Neuropsychobiology, Department of Pharmacology, Ribeirão Preto Medical School of the University of São Paulo (FMRP-USP), Ribeirão Preto, São Paulo, Brazil; Institute of Neuroscience and Behaviour (INeC), Ribeirão Preto, São Paulo, Brazil.
Laboratory of Neuroanatomy and Neuropsychobiology, Department of Pharmacology, Ribeirão Preto Medical School of the University of São Paulo (FMRP-USP), Ribeirão Preto, São Paulo, Brazil; Institute of Neuroscience and Behaviour (INeC), Ribeirão Preto, São Paulo, Brazil; NAP-USP-Neurobiology of Emotions Research Centre (NuPNE), Ribeirão Preto Medical School of the University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Neuroscience. 2015 Jan 22;284:988-997. doi: 10.1016/j.neuroscience.2014.11.001. Epub 2014 Nov 7.
Several lines of evidence indicate that the dorsal hippocampus (dH) and medial prefrontal cortex (mPFC) regulate contextual fear conditioning. The prelimbic (PrL), infralimbic (IL) and the anterior cingulate cortex (ACC) subregions of the mPFC likely play distinct roles in the expression of fear. Moreover, studies have highlighted the role of serotonin (5-hydroxytryptamine, 5-HT)- and γ-aminobutyric acid (GABA)-mediated mechanisms in the modulation of innate fear in the mPFC. The present study characterized dH-mPFC pathways and investigated the role of serotonergic and GABAergic mechanisms of the PrL, IL and ACC-area 1 (Cg1) in the elaboration of contextual fear conditioning using fear-potentiated startle (FPS) and freezing behavior in Rattus norvegicus. The results of neurotracing with microinjections of biotinylated dextran amine into the dH revealed a neural link of the dH with the PrL and ACC. Intra-PrL injections of the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) and the GABAA receptor-selective agonist muscimol reduced contextual FPS and freezing responses. Intra-Cg1 injections of muscimol but not 8-OH-DPAT decreased FPS and freezing responses. However, neither intra-IL injections of a 5-HT1A agonist nor of a GABAA agonist affected these defensive responses. Labeled neuronal fibers from the dH reached the superficial layers of the PrL cortex and spread to the inner layers of PrL and Cg1 cortices, supporting the pharmacological findings. The present results confirmed the involvement of PrL and Cg1 in the expression of FPS and freezing responses to aversive conditions. In addition, PrL serotoninergic mechanisms play a key role in contextual fear conditioning. This study suggests that PrL, IL and Cg1 distinctively contribute to the modulation of contextual fear conditioning.
多条证据表明，背侧海马体（dH）和内侧前额叶皮质（mPFC）调节情境恐惧条件反射。内侧前额叶皮质的前边缘区（PrL）、下边缘区（IL）和前扣带回皮质（ACC）亚区可能在恐惧表达中发挥不同作用。此外，研究强调了血清素（5-羟色胺，5-HT）和γ-氨基丁酸（GABA）介导的机制在调节内侧前额叶皮质先天恐惧中的作用。本研究对背侧海马体-内侧前额叶皮质通路进行了表征，并利用大鼠的恐惧增强惊吓（FPS）和僵住行为，研究了前边缘区、下边缘区和扣带回1区（Cg1）的血清素能和GABA能机制在情境恐惧条件反射形成中的作用。向背侧海马体微量注射生物素化葡聚糖胺进行神经示踪的结果显示，背侧海马体与前边缘区和扣带回之间存在神经联系。在前边缘区内注射5-HT1A受体激动剂8-羟基-2-（二正丙基氨基）四氢萘（8-OH-DPAT）和GABAA受体选择性激动剂蝇蕈醇可降低情境性恐惧增强惊吓和僵住反应。在扣带回1区内注射蝇蕈醇而非8-OH-DPAT可降低恐惧增强惊吓和僵住反应。然而，在下边缘区内注射5-HT1A激动剂或GABAA激动剂均不影响这些防御反应。来自背侧海马体的标记神经纤维到达前边缘皮质的浅层，并延伸至前边缘区和扣带回1区皮质的内层，支持了药理学研究结果。本研究结果证实了前边缘区和扣带回1区参与了对厌恶条件的恐惧增强惊吓和僵住反应的表达。此外，前边缘区血清素能机制在情境恐惧条件反射中起关键作用。本研究表明，前边缘区、下边缘区和扣带回1区对情境恐惧条件反射的调节有不同贡献。
