Mechanisms Underlying Learning Deficits Caused by Paternal Cocaine Taking

 描述（由申请人提供）：越来越多的证据表明，环境信息可以遗传。因此，哺乳动物生殖系中的表观遗传变化可以作为环境扰动的跨代载体。可卡因成瘾在美国仍然是一个严重的健康问题，长期使用可卡因与神经认知缺陷有关。然而，目前尚不清楚父母滥用可卡因是否会导致后代认知功能下降。本研究将利用大鼠可卡因成瘾模型，研究父亲服用可卡因对后代记忆形成的影响。我们发现，可卡因暴露的父亲（父亲）的后代和孙子有空间学习障碍和受损的海马突触可塑性。在具体目标1中，我们假设增加海马中的NMDA受体信号传导将改善由父亲服用可卡因引起的突触可塑性和学习缺陷。在具体目标2中，我们将研究可卡因暴露公畜后代海马中的基础突触功能和NMDA受体信号传导。两者合计，这项建议将试图阐明的机制，学习缺陷，是由父亲服用可卡因。

 DESCRIPTION (provided by applicant): A growing body of evidence indicates that environmental information can be inherited. Thus, epigenetic changes in the mammalian germline can act as a transgenerational carrier of environmental perturbations. Cocaine addiction remains a significant health problem in the United States and chronic cocaine use is associated with neurocognitive deficits. However, it remains unclear whether cocaine abuse in parents translates to reduced cognitive function in their offspring. This proposal will focus on th effects of paternal cocaine taking on memory formation in offspring using a rat model of cocaine addiction. We found that the offspring and grand-offspring of cocaine-exposed fathers (sires) have spatial learning deficits and impaired hippocampal synaptic plasticity. In Specific Aim 1, we hypothesize that increasing NMDA receptor signaling in the hippocampus will ameliorate synaptic plasticity and learning deficits caused by paternal cocaine taking. In Specific Aim 2, we will investigate basal synaptic function and NMDA receptor signaling in the hippocampus of the descendants of cocaine-exposed sires. Taken together, this proposal will attempt to illuminate the mechanisms underlying learning deficits that are caused by paternal cocaine taking.