The prefrontal cortex: responses to threat in early life

描述（由申请人提供）：幼龄动物有能力以特定年龄的方式对威胁刺激作出反应。然而，关于适应性恐惧反应背后的神经基质，我们所知甚少。在成年动物中，前额皮质在调节情绪方面起着重要作用。特别是，前额叶皮层的内侧部分通过投射到杏仁核和导水管周围灰质来调节对威胁的行为反应。本应用程序的目的是确定内侧前额叶皮层及其投影区域在幼龄动物对威胁的适应性反应中的作用。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育中的情绪行为。为了验证这一假设，将三个不同年龄的年轻大鼠暴露在特定年龄的威胁和非威胁情境中，并确定内侧前额叶皮层及其投射区域在这些情境下的恐惧反应中的作用。有三个具体目标。1. 内侧前额叶皮层的分支在药理学上失活，并确定对威胁和非威胁的行为反应的影响。内侧前额叶皮层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。神经元激活是通过即时早期基因表达来评估的。2. 刺激内侧前额叶皮层的细分，评估对威胁和非威胁行为反应的影响，以及对杏仁核和导水管周围灰质激活的影响。3. 为了确定三个年龄段差异反应的神经基础，我们评估了威胁和非威胁情况下内侧前额叶皮层分支中gaba能中间神经元的激活。该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。了解前额皮质在发育中的功能是至关重要的，因为前额皮质回路的早期改变与以后生活中出现精神病理（如焦虑症）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.