Methamphetamine Effects on Prefrontal Cortical PV+ Interneurons and Resulting Cognitive Deficits

摘要 这项多样性补充支持是为Antonieta Lavin博士实验室的Monserrat Armenta-Resendiz博士提供的 在南卡罗来纳医科大学，由Carmela Reichel博士和Tom Jhou博士提供额外指导。 Armenta-Resendiz博士是一名拉丁裔女性，她的目标是成为一名独立科学家，该领域将 毒品成瘾、认知缺陷和性别差异。Armenta-Resendiz博士需要获得 额外的技术技能，增强她的专业技能，并发展学术概况，以确保她处于 具有竞争力的职位申请R型创始和终身教职轨道的学术职位。 亲本R01(DA 054589-01)的目的是确定甲基水杨酸对酶活性的影响。 皮质小白蛋白阳性快速放电中间神经元(PV+FSIS)及由此引起的E-I比值的变化。这个 中心假设--基于强有力的初步数据和文献--是冰毒治疗引发认知 通过激活PV+FSIS的D1R，导致PFC内GABA能突触传递增加所致的缺陷。这个 提议的理由是，实验将产生与理解有关的基本知识 冰毒引起的前额叶低的细胞和突触机制，并将提供新的见解 前额叶皮质E-I平衡的基本机制。我们将通过以下方式检验中心假设 追求以下具体目标：目标1将确定PV+FSIS在冰毒诱导的认知中的作用 赤字。目标2将确定是否需要PFC PV+FSIS中的D1R信号用于冰毒诱导 增强GABA能传递。目标3将确定PFC PV+FSIS中的D1R信令是否 是冰毒引起的认知障碍和冰毒恢复所必需的。这项拟议的研究具有重要意义 因为它将填补有关前额叶低反应潜在机制的一个基本知识空白。 冰毒成瘾及精神刺激剂对大脑皮层PV+FSIS活性的影响此外， 从拟议的实验中获得的知识将有助于开发有效的治疗方法来改善药物- 相关的认知缺陷，并可以提供新的见解，潜在的基本机制的额叶下 其他神经精神疾病。 为了支持Armenta-Resendiz博士的培训，我们制定了一个额外的目标，该目标扩展和 补充父RO1。1.她将实施DA和谷氨酸的纤维光度评估 METH和SAL雌雄大鼠在认知任务(暂时性)执行过程中的PFC感受器 顺序记忆)在体内。该培训计划将为Armenta-Resendiz博士提供更多的光纤技能 光度学、性防御和行为。她还将接受来自不同团队的额外指导，并 培训以确保她为自己选择的职业道路做好了充分的准备。

SUMMARY This Diversity Supplement support is for Dr. Monserrat Armenta-Resendiz in the laboratory of Dr Antonieta Lavin at the Medical University of South Carolina with additional mentorship by Dr. Carmela Reichel and Tom Jhou. Dr. Armenta-Resendiz is a Latina woman whose goal is to become an independent scientist in a field that will intersect drug addiction, cognitive deficits and sex differences. Dr Armenta-Resendiz needs to acquire additional technical skills, enhance her professional skills, and develop an academic profile to ensure she is in a competitive position to apply for R type founding and tenure track academic positions. The objective of the parent R01 (DA 054589-01) is is to identify the effects of METH-SA on the activity of cortical parvalbumin positive fast spiking interneurons (PV+FSIs) and the resulting changes in E-I ratio. The central hypothesis- informed by strong preliminary data and literature- is that METH treatment elicits cognitive deficits due to an increase in GABAergic synaptic transmission in the PFC via D1R activation of PV+FSIs. The proposal’s rationale is that the experiments will yield fundamental knowledge pertaining to the understanding of the cellular and synaptic mechanisms underlying hypofrontality induced by METH and will provide new insights into the basic mechanisms governing E-I balance in the prefrontal cortex. We will test the central hypothesis by pursuing the following specific aims: Aim 1 will determine the role of PV+FSIs in METH-induced cognitive deficits. Aim 2 will determine whether D1R signaling in PFC PV+FSIs is required for METH-induced enhancements of GABAergic transmission. Aim 3 will determine whether D1R signaling in PFC PV+FSIs is required for METH SA-induced cognitive deficits and METH reinstatement. The proposed research is significant because it will fill a fundamental gap in knowledge pertaining to the mechanisms underlying hypofrontality in METH-addiction and the effects of the psychostimulant in the activity of cortical PV+FSIs. Furthermore, the knowledge obtained from the proposed experiments will help to develop effective treatments to ameliorate drug- related cognitive deficits and can provide new insights into the basic mechanisms underlying hypofrontality in other neuropsychiatric conditions. To support the training of Dr Armenta-Resendiz, we have developed an additional aim that extends and complements the parent RO1. 1. She will implement fiber photometry assessments of DA and Glutamate sensors in the PFC of METH and SAL male and female rats during the performance of a cognitive task (Temporal Order Memory) in vivo. This training program will provide Dr Armenta-Resendiz with additional skills in fiber photometry, sex defenses and behavior. She will also receive additional mentorship from a diverse team and trainings to ensure she is fully equipped for her chosen career path.