Aging and CA1 Neural Modeling of Trace Fear Conditioning

衰老和微量恐惧调节的 CA1 神经模型

基本信息

批准号：
6401185
负责人：
Matthew David McEchron
金额：
$ 7.03万
依托单位：
PENNSYLVANIA STATE UNIV HERSHEY MED CTR
依托单位国家：
美国
项目类别：
财政年份：
2001
资助国家：
美国
起止时间：
2001-09-15 至 2002-08-31
项目状态：
已结题

项目摘要

This pilot study will address the Neural Research Objective and will examine the neural firing pattern of CA1-hippocampal neurons is aged rats performing a learning task called trace fear conditioning. Auditory trace fear conditioning is a learning task where animal are required to associate an auditory conditioned stimulus (CS) and a fear-producing shock-unconditioned stimulus (US) that are separated by a long empty 20- second trace interval. My work has shown that association of the CS and US in trace fear conditioning in young animals is dependent on cells in the dorsal hippocampus. Pilot data suggest that a proportion of aged rats (5 of 10) are impaired in the trace fear conditioning task. My most recent neurophysiological work has demonstrated that single neurons in the CA1-hippocampus of young animals show a very robust learning-related representation of the duration of the trace interval following trace fear conditioning. Specifically, on CS-alone trails following trace fear conditioning that CA1 neurons showed a time-locked firing pattern that represented the duration of the 20-second trace interval used on previous CS-trace-US trails. /there have been only a limited number of neurophysiological studies which have examined how aging affects the neuronal encoding of learning-related information. This is partly because it has been so difficult to describe neuronal patterns of activity in the young normal brain that confidently represent learned information. However, the robust neuronal representation of the trace interval obtained during trace fear conditioning should provide an excellent tool for determining if the CA1 neurons of aged animals show altered neuronal encoding of learning-related information. Therefore, this pilot study will examine the CA1-neuronal firing pattern of young and aged rats during trace feat conditioning. Rats of three different aged groups (4,21, and 26 months) will receive two trace fear conditioning sessions where each trail consists of an auditory tone-CS and a fear-producing shock-US which are separated by a very long 20-second trace interval. Single neurons will be recorded extracellularly from Ca1 during the trace fear conditioning task to determine if neurons in aged rats encode the duration of the trace interval, and to examine how the encoding o the trace interval is related to aging-related learning deficits. This work will provide important for later studies examining how other structures in the fear conditioning circuit (e.g., amygdala, dentate, entorhinal cortex) contribute to deficient encoding of information in the CA1 of aged animals.

这项试点研究将解决神经研究目标，并将检查CA1-HAPPOCAMPAL神经元的神经发射模式是老年大鼠，执行了一项名为Trace Fear Recestion的学习任务。听觉痕量恐惧条件是一项学习任务，需要动物将听觉条件刺激（CS）和产生恐惧的冲击无条件刺激（US）相关联，这些刺激（US）被长时间空的20秒痕量间隔分开。我的工作表明，CS和我们在年轻动物的恐惧条件下的关联取决于背侧海马中的细胞。试点数据表明，在痕量恐惧调节任务中，年龄大鼠的比例（10中的5个）受到了损害。我最近的神经生理学工作表明，年轻动物的Ca1-Hampocampus中的单个神经元表现出非常强大的与学习相关的表示，在痕量恐惧条件下，痕量间隔的持续时间非常强。具体而言，在痕量恐惧条件下，CA1神经元显示出时间锁定的射击模式，该图案代表了以前的CS-Trace-US步道上使用的20秒痕量间隔的持续时间。 /只有有限数量的神经生理研究研究了衰老如何影响与学习相关信息的神经元编码。这部分是因为很难描述年轻的正常大脑中的神经元模式，以自信地代表学习的信息。但是，在痕量恐惧条件过程中获得的痕量间隔的稳健神经元表示应该为确定老年动物的CA1神经元是否显示出改变与学习相关信息的神经元编码的出色工具。因此，这项试验研究将检查痕量壮举调节期间的年轻大鼠和老年大鼠的CA1神经元放电模式。三个不同老年组（4,21个和26个月）的大鼠将获得两个痕量恐惧条件会话，每条路径由听觉音调CS和产生恐惧的震动 - US组成，这些冲击是由很长的20秒痕量间隔组成。在痕量恐惧调节任务中，将从CA1细胞外记录单神经元，以确定年龄大鼠中的神经元是否编码痕量间隔的持续时间，并检查痕量间隔与衰老相关的学习缺陷的编码o如何相关。这项工作将为以后的研究提供重要的研究，以研究恐惧条件回路中的其他结构（例如杏仁核，牙本质，内嗅皮层）如何有助于不足的老年动物CA1信息编码。