Functional Neurobiology of the Retrosplenial Cortex During Associative Learning

描述(申请人提供)：大多数活动发生在视觉、听觉、触觉和嗅觉刺激丰富的环境中。动物必须吸收大量信息，才能了解重要的、与行为相关的事件。复杂或结构联想学习需要在不同的、同时呈现的刺激之间形成相互关系。这种类型的学习传统上被认为发生在大脑的皮质-海马区网络中，但编码这种基本学习形式的特定路径和区域尚未解决。本研究的主要假设是，脾后皮质(RSP)及其与纹后皮质的联系对结构联想学习至关重要。总之，这些目标旨在研究RSP对行为的神经活动、功能回路和特定贡献。目标1中的实验提出了一个问题：RSP是学习的积极中介吗？在情境恐惧条件作用(一种结构联想学习)后，将测量RSP中神经元的激活。行为诱导的神经活动将通过量化即刻早期基因Arc(活动相关细胞骨架蛋白)的亚区特异性表达来评估，该基因已被证明在突触可塑性中起着重要作用。这些研究有可能证实，在联想学习过程中，RSP是感觉信息的中介，而不仅仅是一条管道。具体目标2专注于了解动物在学习时，RSP的哪些亚区与其他“认知”脑区进行通信。在这些研究中，逆行追踪将与即刻早期基因表达相结合，以确定在厌恶恐惧条件作用后最显著激活的RSP通路。在目标3中，将采用结构学习的演示测验--负模式任务来明确检验RSP对于涉及多个同时呈现的刺激的加工的联想学习是必要的这一假设。这项建议解决了关于RSP认知的神经基础的基本问题，RSP是一个与阿尔茨海默病和精神分裂症等病理疾病密切相关的大脑区域。在健康的大脑中阐明参与学习的神经通路可能被证明特别有助于识别可能在神经退行性疾病和认知功能心理障碍中受到最大影响的目标区域。

DESCRIPTION (provided by applicant): Most events occur in environments that are rich with visual, auditory, tactile and olfactory stimuli. Animals must assimilate vast amounts of information to learn about important, behaviorally relevant events. Complex or configural associative learning is that which requires the formation of inter-relationships among different, simultaneously presented stimuli. This type of learning has traditionally been considered to occur within cortico-hippocampal networks in the brain, but the particular pathways and regions that encode this essential form of learning are unresolved. The overarching hypothesis of this research is that the retrosplenial cortex (RSP) and its connections with the postrhinal cortex are critical for configural associative learning. Together, these aims are designed to investigate the neural activity, functional circuitry and specific contribution of RSP to behavior. The experiments in Aim 1 pose the question: Is RSP an active mediator of learning? Neuronal activation in RSP will be measured in rats following contextual fear conditioning (a form of configural associative learning). Behaviorally-induced neural activity will be assessed by quantifying the sub-region specific expression of the immediate early gene, Arc (activity related cytoskeletal protein), which has been shown to play a prominent role in synaptic plasticity. These studies have the potential to establish that RSP is a mediator, rather than simply a conduit, of sensory information during associative learning. Specific Aim 2 is focused on understanding which subregions of RSP communicate with other "cognitive" brain regions when an animal is learning. For these studies, retrograde tracing will be combined with immediate early gene expression to identify RSP pathways that are most prominently activated following aversive fear conditioning. In aim 3, the negative patterning task, which is the demonstrative test of configural learning, will be employed to explicitly test the hypothesis that RSP is necessary for associative learning that involves the processing of multiple, simultaneously presented stimuli. This proposal addresses basic questions about the neural basis of cognition in RSP, a brain region that is closely associated with pathological conditions such as Alzheimer's disease and Schizophrenia. Elucidating the neural pathways involved in learning in healthy brains could prove to be especially useful in identifying target regions that may be most affected in neurodegenerative and psychological disorders of cognitive function.