Cortico-hippocampal contributions to context and extinction learning.

皮质海马对情境和灭绝学习的贡献。

• 批准号: 8780906
• 负责人: Travis Todd
• 金额: $ 4.99万
• 依托单位: DARTMOUTH COLLEGE
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-01 至 2017-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8780906
• 关键词: Address; Alzheimer' s Disease; Animal Experiments; Animal Model; Animals; Anxiety; Auditory; Behavior; Beryllium; Brain; Brain region; Clinical Treatment; Complex; Cues; Data; Designer Drugs; Development; Disease; Environment; Event; Extinction (Psychology); Food; Fright; Hippocampus (Brain); Human; Individual; Lead; Learning; Memory; Mental disorders; Organism; Outcome; Pathway interactions; Phase; Phobic anxiety disorder; Post-Traumatic Stress Disorders; Procedures; Process; Rattus; Recovery; Relapse; Research; Retrieval; Role; Schizophrenia; Shock; Staging; Stimulus; Sum; Tactile; Techniques; Testing; Time; Update; Vacuum; Visual; Work; clinical practice; conditioned fear; experience; foot; innovation; insight; learned behavior; learning extinction; novel; public health relevance; receptor; relating to nervous system; research study; response

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.

描述（由申请人提供）：学习过程允许生物体（包括人类）调整其行为以适应环境的变化，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。为了成功地了解生物学上重要的事件（例如，食物或猎物的存在），动物必须首先将环境的各个特征联合收割机组合成一个综合的记忆，或“上下文”表示。当代研究表明，这种类型的学习发生在大脑中的皮质-海马网络中。然而，对于学习背景至关重要的特定区域的确切途径和个体功能尚未完全解决。这个建议的首要假设是，restrosplenial皮质（RSP）是必不可少的形成整合的上下文表示，和后嗅皮质（POR）是必不可少的更新这些记忆。这个提议解决了关于情境恐惧学习的神经基质的未回答的问题（具体目标1）。它还涉及RSP和POR在恢复到先前熄灭的恐惧线索中的功能作用。恐惧消退是特定于情境的，恢复可以是重新经历令人厌恶的事件（即，恢复;具体目标2）或当自恐惧消退发生以来已经过了相当长的时间时（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暂时失活：由设计药物独家激活的设计受体（DREADD）。这种暂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。总而言之，这项建议研究了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：PTSD;焦虑相关障碍，恐惧症）。此外，已知RSP在人类疾病如精神分裂症和阿尔茨海默病中受损。因此，研究RSP和POR在恐惧学习和恐惧消退过程中的作用，可以证明对人类的临床实践特别有用。