The prefrontal cortex: responses to threat in early life

描述（由申请人提供）：婴儿动物有能力以特定年龄的方式对威胁性刺激做出反应。然而，人们对适应性恐惧样反应背后的神经基质知之甚少。前额叶皮层在成年动物的情绪调节中起着重要作用。特别是，前额叶皮层的内侧部分通过向杏仁核和中脑导水管周围灰质的投射来调节对威胁的行为反应。这个应用程序的目的是确定的作用，内侧前额叶皮层和它的投影区在适应性反应的威胁在年轻的动物。核心假设是，内侧前额叶皮层的分支通过促进对威胁的恐惧反应或抑制对非威胁的恐惧反应来调节早期发展中的情绪行为。为了验证这一假设，三个不同年龄的年轻大鼠暴露于特定年龄的威胁性和非威胁性的情况下，内侧前额叶皮层及其投射区在这些情况下的恐惧样反应的作用是确定的。有三个具体目标。1.内侧前额叶皮层的分区被激活，并确定对威胁和非威胁的行为反应的影响。内侧前额叶皮质的输出功能是通过评估其投射区杏仁核和导水管周围灰质的激活来确定的。通过即刻早期基因表达评估神经元活化。2.刺激内侧前额叶皮层的分区，评估对威胁和非威胁的行为反应以及对杏仁核和导水管周围灰质的激活的影响。3.为了确定在三个年龄的差异反应的神经基础，GABA能中间神经元的内侧前额叶皮层的分区的威胁和非威胁的情况下进行评估的激活。这项研究将为内侧前额叶皮层在早期生活中的情绪调节中的双重作用提供强有力的证据。了解前额叶皮层在发育过程中的功能至关重要，因为前额叶皮层电路的早期改变与日后患焦虑症等精神病理学的风险增加有关。

DESCRIPTION (provided by applicant): Infant animals have the ability to respond in age-specific ways to threatening stimuli. Little is known, however, about the neural substrate underlying adaptive fear-like responses. The prefrontal cortex plays a major role in the regulation of emotion in adult animals. In particular, the medial part of the prefrontal cortex modulates behavioral responses to threat through projections to the amygdala and the periaqueductal gray. The objective of this application is to determine the role of the medial prefrontal cortex and its projection areas in adaptive responses to threat in young animals. The central hypothesis is that subdivisions of the medial prefrontal cortex modulate emotional behavior across early development by either facilitating fear-like responses to threat or by inhibiting fear-like responses to non-threat. To test this hypothesis, young rats of three different ages are exposed to age-specific threatening and non-threatening situations and the role of the medial prefrontal cortex and its projection areas in fear-like responses to these situations is determined. There are three specific aims. 1. Subdivisions of the medial prefrontal cortex are pharmacologically inactivated and effects on behavioral responses to threat and non-threat are determined. Medial prefrontal cortex output function is determined by assessing activation in its projection areas, the amygdala and the periaqueductal gray. Neuronal activation is assessed by immediate early gene expression. 2. Subdivisions of the medial prefrontal cortex are stimulated and effects on behavioral responses to threat and non-threat and on the activation of amygdala and periaqueductal gray are assessed. 3. To determine the neural basis of differential responsivity at the three ages, the activation of GABAergic interneurons in subdivisions of the medial prefrontal cortex by threatening and non-threating situations is assessed. The proposed study will provide strong evidence for the dual role of the medial prefrontal cortex in emotion regulation across early life. Understanding prefrontal cortex function in development is crucial because early alterations of prefrontal cortex circuitry are associated with increased risk for the development of psychopathologies such as anxiety disorders later in life.