Fondazione Santa Lucia, Instituto di Ricovero e Cura a Carattere Scientifico, I-00179 Rome, Italy.
Rev Neurosci. 2011;22(3):303-15. doi: 10.1515/RNS.2011.031.
Discovering the basic mechanisms in fear encoding and expression is important in many fields, including psychology, sociology, medicine, and neuroscience. Effective treatment for fear-based pathology depends on understanding how fear is learned and regulated. Among the molecular systems required for fear learning and amygdalar synaptic plasticity, brain derived neurtrophic factor (BDNF) and its high affinity receptor Ntrk2/TrkB have been shown to play essential roles. Therefore, we will focus this review on three main aspects; first of all, the impact of Bdnf polymorphism on fear related characteristics in humans and animal models. Secondly, we will discuss BDNF-TrkB activity regulation by epigenetic, transcriptional and post-translational events, and finally we will discuss TrkB-BDNF signalling in fear learning. BDNF-TrkB and the signalling activated in this particular form of plasticity are becoming crucial players in fear learning and memory thus highlighting these molecules as potential therapeutic targets in fear-related pathologies.
发现恐惧编码和表达的基本机制在许多领域都很重要,包括心理学、社会学、医学和神经科学。基于恐惧的病理学的有效治疗取决于对恐惧是如何习得和调节的理解。在恐惧学习和杏仁核突触可塑性所需的分子系统中,脑源性神经营养因子(BDNF)及其高亲和力受体 Ntrk2/TrkB 已被证明发挥着重要作用。因此,我们将重点关注三个主要方面;首先,Bdnf 多态性对人类和动物模型中与恐惧相关特征的影响。其次,我们将讨论 BDNF-TrkB 活性的调控,包括表观遗传、转录和翻译后事件,最后,我们将讨论 TrkB-BDNF 信号在恐惧学习中的作用。BDNF-TrkB 及其在这种特定形式的可塑性中激活的信号转导正在成为恐惧学习和记忆的关键参与者,从而突出这些分子作为与恐惧相关疾病的潜在治疗靶点。