de Lima Miguel Antonio Xavier, Baldo Marcus Vinicius C, Canteras Newton Sabino
Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, Av. Lineu Prestes, 2415, São Paulo, SP, 05508-000, Brazil.
Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, 05508-000, Brazil.
Brain Struct Funct. 2017 Jan;222(1):113-129. doi: 10.1007/s00429-016-1204-2. Epub 2016 Mar 7.
Previous studies from our group have shown that cytotoxic lesions in the ventral portion of the anteromedial thalamic nucleus (AMv), one of the main targets of the hypothalamic predator-responsive circuit, strongly impairs contextual fear responses to an environment previously associated with a predator. The AMv is in a position to convey information to cortico-hippocampal-amygdalar circuits involved in the processing of fear memory. However, it remains to be determined whether the nucleus is involved in the acquisition or subsequent expression of contextual fear. In the present investigation, we addressed this question by inactivating the rat AMv with muscimol either prior to cat exposure or prior to exposure to the cat-related context. Accordingly, AMv pharmacological inactivation prior to cat exposure did not interfere with innate fear responses, but it drastically reduced contextual conditioning to the predator-associated environment. On the other hand, AMv inactivation prior to exposure to the environment associated with the predator threat did not affect contextual fear responses. The behavioral results were further supported by the demonstration that AMv inactivation prior to cat exposure also blocked the activation of sites critically involved in the expression of anti-predatory contextual defensive responses (i.e., the dorsal premammillary nucleus and the dorsolateral periaqueductal gray) in animals exposed to the predator-associated context. The AMv projections were also examined, and the results of this investigation outline important paths that can influence hippocampal circuitry and raise new ideas for anterior thalamic-hippocampal paths involved in emotional learning.
我们小组之前的研究表明,丘脑前内侧核腹侧部分(AMv)存在细胞毒性损伤,该区域是下丘脑捕食者反应回路的主要靶点之一,这会严重损害对先前与捕食者相关环境的情境恐惧反应。AMv能够将信息传递给参与恐惧记忆处理的皮质-海马-杏仁核回路。然而,该核团是否参与情境恐惧的习得或后续表达仍有待确定。在本研究中,我们通过在大鼠接触猫之前或接触与猫相关的环境之前用蝇蕈醇使AMv失活来解决这个问题。因此,在接触猫之前对AMv进行药物失活并不干扰先天恐惧反应,但它显著降低了对与捕食者相关环境的情境条件作用。另一方面,在接触与捕食者威胁相关的环境之前对AMv进行失活并不影响情境恐惧反应。行为结果进一步得到了以下证据的支持:在接触猫之前对AMv进行失活也会阻断暴露于与捕食者相关环境的动物中参与反捕食情境防御反应表达的关键部位(即乳头体背侧核和导水管周围灰质背外侧)的激活。我们还研究了AMv的投射,这项研究的结果勾勒出了可以影响海马回路的重要路径,并为参与情绪学习的丘脑前-海马路径提出了新的想法。