Functional Properties of the Lateral Entorhinal Cortex in Learning and Aging

项目摘要/摘要 衰老通常与学习和记忆障碍有关。然而，一些老年人仍然没有 任何损害。目前的项目致力于研究神经生物学机制。 衰老相关的损害以及有损害的人和没有损害的人(老年性受损-AI)的区别 (老年未受损-AU)。以前的研究主要集中在海马体上，海马体是 记忆的形成。目前的项目将集中在内嗅皮层(EC)，这是 记忆是大脑皮层和海马体之间的中继站。欧共体不仅是 对支持记忆很重要，但也是与衰老相关的重大变化的场所。例如，在 正常衰老时，EC容量与较差的记忆性能直接成反比。阿尔茨海默氏症 疾病是一种神经退行性疾病，其主要风险因素是年龄增加，最初表现为 欧盟委员会。目前的项目将侧重于欧共体的横向分工。建议横向EC支持 时间联想记忆的形成，这是一项许多老年人受到损害的任务。这些 越来越多的证据表明，LEC内存在神经生物学变化，这支持 学习和随着年龄增长而改变的神经生理学可能是无法经历这些变化的基础， 从而导致学习障碍。因此，目前的项目试图确定生物物理变化 发生在成功学习(Y和AU)的幼年和老年动物的LEC神经元中 这不能(人工智能)。该项目将专注于通过穿透路径投射到 齿状回，作为穿支路径构成三突触环的第一步，是 海马体中的记忆形成。虽然之前的研究已经将电生理特征描述为 对于LEC中的神经元，穿支通路神经元的身份尚未确定。这就做, 因此，首先通过将逆行荧光示踪剂注射到 幼年和老年动物的齿状回(目标1)。荧光示踪剂将确认 并允许在全细胞电流钳记录期间进行靶向，从而允许确认 电生理图谱。在全细胞记录期间，我还将像以前一样测量神经元的兴奋性 研究已经确定，与衰老相关的海马区神经元兴奋性的变化 阻止了老年动物的成功学习。然后我将训练年轻的成年人和老年的动物在时间上 联想学习任务，以测量穿支路径中与学习相关的兴奋性变化 神经元(目标2)。录音将揭示学习是如何在Y和AU动物的LEC中得到支持的，而且 找出阻止人工智能动物成功学习的机制。这项研究的结果将提供 作为减轻衰老相关学习障碍和痴呆症的潜在疗法的目标。

Project Summary/Abstract Aging is often associated with learning and memory impairments. Yet, some aged individuals remain free of any impairment. The current project seeks to investigate the neurobiological mechanisms that underlie the aging-related impairments and what separates those with impairments (aged impaired--AI) from those without (aged unimpaired--AU). Previous research has focused on the hippocampus, a major region necessary for memory formation. The current project will focus on the entorhinal cortex (EC), another important region for memory, as it serves as the relay station between cortical regions and the hippocampus. The EC is not only important for supporting memory, but is also a site for major aging-related changes. For example, within normal aging, EC volume is directly inversely correlated with poorer memory performance. Alzheimer’s disease, a neurodegenerative disorder whose major risk factor is increasing age, initially manifests itself within the EC. The current project will focus on the lateral division of the EC. The lateral EC is suggested to support the formation of temporal associative memory, a task on which many aged individuals are impaired. These converging pieces of evidence suggest the presence of neurobiological changes within the LEC that support learning and that altered neuronal physiology with aging may underlie the inability to undergo those changes, thus resulting in learning deficits. The current project, therefore, seeks to identify the biophysical alterations that occur in LEC neurons from young and aged animals that successfully learn (Y and AU) and from those that cannot (AI). The project will focus on changes within the neurons that project via the perforant path to the dentate gyrus, as the perforant path makes up the first step of the trisynaptic loop, the classic circuit for memory formation in the hippocampus. While previous studies have electrophysiologically characterized the neurons of the LEC, the identity of the perforant path neuron has not yet been definitively identified. I will, therefore, first establish the identity of the perforant path neuron by injecting a retrograde fluorescent tracer into the dentate gyrus of young and aged animals (Aim 1). The fluorescent tracer will confirm the morphology of the neuron and also allow for targeting during whole-cell current clamp recordings, allowing for confirmation of the electrophysiological profile. During whole cell recordings, I will also measure neuronal excitability, as previous research has determined that aging-related changes in neuronal excitability within the hippocampus have prevented successful learning in aged animals. I will then train young adult and aged animals on a temporal associative learning task in order to measure learning-related changes in excitability in the perforant path neuron (Aim 2). Recordings will reveal how learning is supported in the LEC of Y and AU animals and also identify mechanisms that prevent successful learning in AI animals. The results of this study will provide a target for potential therapeutics in alleviating aging-related learning deficits and dementia.