Cortico-hippocampal contributions to context and extinction learning.

描述(申请人提供)：学习过程允许有机体(包括人类)使其行为适应环境的变化，因此对生存至关重要。然而，学习不是在真空中进行的。事实上，大多数学习经历都发生在由视觉、听觉、嗅觉和触觉刺激组成的复杂环境中。为了成功地了解发生在特定环境中的具有生物学意义的事件(例如，食物或猎物的存在)，动物必须首先将环境的个别特征结合到一个完整的记忆中，即“背景”表征中。当代研究表明，这种类型的学习发生在大脑的皮质-海马区网络中。然而，学习背景所必需的特定区域的确切途径和个别功能尚未完全解决。这一建议的主要假设是，背侧脾皮质(RSP)对于形成完整的语境表征是必不可少的，而后皮质(POR)对于更新这些记忆是必不可少的。这项建议解决了关于情境恐惧学习的神经基础(具体目标1)的悬而未决的问题。它还讨论了RSP和POR在恢复先前消失的恐惧线索的恐惧中的功能作用。恐惧消退取决于具体情况，恢复可以通过重新经历令人厌恶的事件(例如，恢复；具体目标2)，或者在恐惧消退发生后很长一段时间过去时(即，自发恢复；具体目标3)。在所有研究中，RSP和POR将使用一种新的创新技术被暂时灭活：设计师受体仅由设计师药物(DREADD)激活。这种临时失活将允许在编码和/或检索过程中隔离这些区域的作用。总之，这项建议考察了RSP和POR在情境学习和恐惧消退中的作用，这两个过程在人类几种精神疾病的发展和随后的治疗中非常重要(例如，创伤后应激障碍：创伤后应激障碍；焦虑相关障碍，恐惧症)。此外，众所周知，RSP在精神分裂症和阿尔茨海默病等人类疾病中受到损害。因此，研究RSP和POR在恐惧学习和恐惧消退过程中的作用，可能会被证明对人类的临床实践特别有用。

DESCRIPTION (provided by applicant): Learning processes allow organisms (including humans) to adapt their behavior to changes in the environment, and are thus crucial for survival. However, learning does not take place in a vacuum. Indeed, most learning experiences occur within complex environments composed of visual, auditory, olfactory, and tactile stimuli. To successfully learn about biologically significant events (e.g., the presence of food or prey) that occur within particular environments, animals must first combine individual features of the environment into an integrated memory, or "context" representation. Contemporary research suggests that this type of learning occurs within cortico-hippocampal networks in the brain. However, the exact pathways and individual functions of particular regions essential for learning about contexts have not been fully resolved. The overarching hypothesis of this proposal is that the restrosplenial cortex (RSP) is essential for forming integrated context representations, and that the postrhinal cortex (POR) is essential for updating these memories. This proposal addresses unanswered questions about the neural substrates of contextual fear learning (Specific Aim 1). It also addresses the functional role of RSP and POR in the recovery of fear to a previously extinguished fear cue. Fear extinction is context specific, and recovery can result either from re-experiencing the aversive event (i.e., reinstatement; Specific Aim 2) or when a significant amount of time has passed since fear extinction occurred (i.e., spontaneous recovery; Specific Aim 3). In all studies, RSP and POR will be temporally inactivated using a new and innovative technique: Designer Receptors Exclusively Activated by Designer Drugs (DREADDs). This temporary inactivation will allow for isolation of the role of these regions during encoding and/or retrieval processes. In sum, this proposal examines the role of RSP and POR in context learning and fear extinction, two processes that are important in the development and subsequent treatment of several mental illnesses in humans (e.g., post-traumatic stress disorder: PTSD; anxiety related disorders, phobias). Further, the RSP is known to be compromised in human disorders such as schizophrenia and Alzheimer's disease. Therefore, investigating the role of RSP and POR, during both fear learning and fear extinction, could prove to be especially informative to clinical practice in humans.