Neurochem Chip: Methodology to Study Untethered Rats

Neurochem 芯片：研究不受束缚的大鼠的方法

• 批准号: 7252437
• 负责人: Greg A. Gerhardt
• 金额: $ 41.17万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-30 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7252437
• 关键词: Acetylcholine; Address; Adult; Animals; Basic Science; Behavior; Bite; Brain; Ceramics; Characteristics; Choline; Corpus striatum structure; Development; Disease model; Drug abuse; Electrodes; Enzymes; Extracellular Space; Film; Freedom; Glutamates; Goals; Grant; Hippocampus (Brain); Hybrids; Implant; In Vitro; Measures; Medical Device; Methodology; Microdialysis; Microelectrodes; Miniaturization; Monitor; Movement; Mus; Neurotransmitters; Noise; Numbers; Performance; Polychlorinated Biphenyls; Prefrontal Cortex; Property; Purpose; Rattus; Research Personnel; Screening procedure; Series; Signal Transduction; Site; Staging; Surface; System; Techniques; Technology; Work; awake; base; data acquisition; design; drug of abuse; gamma-Aminobutyric Acid; improved; in vivo; instrumentation; miniaturize; neurochemistry; neurotransmitter release; uptake

DESCRIPTION (provided by applicant): This Stage II CEBRA application involves the development of Neurochem Chip microelectrodes for neurochemical recordings of neurotransmitter release in rats and mice. The long-term goals of this project are to develop Neurochem Chips for rapid in vivo recordings of glutamate, GABA, acetylcholine and choline in the CNS of freely moving rats and mice. In developing the technologies, we will first implement and improve the technologies of Neurochem Chips in rats and mice. First, we plan to optimize the recording approaches in the anesthetized rat and mouse. This will involve microelectrode development in corporation with Thin Film Technologies, Hybrid Circuits, Inc., and Cleveland Medical Devices, Inc. Instrumentation development will occur in cooperation with PCB Assembly, Inc. We will carry out extensive in vitro and in vivo recordings of glutamate, GABA, choline and acetylcholine release and uptake in the prefrontal cortex, striatum and hippocampus of anesthetized rats. There are numerous microelectrode, instrumentation, and recording details that must first be optimized to develop reliable Neurochem Chips. These microelectrodes recordings will be compared with microdialysis measures of glutamate and choline, to try and further validate the techniques. As this grant progresses, the refined and adapted technologies will be applied to studies in awake behaving rats and mice. Freely moving tethered systems will be developed for 4-channel measures in awake rats and 2-channel recordings in mice. In addition, a biotelemetric system will be developed to record from rats with a totally untethered system. This should contribute to 1) increased signal-to-noise of the recordings, 2) increased freedom of movement of the rats, and 3) the potential for monitoring large numbers of rats. The major goal of these studies is to develop Neurochem Chips that are reliable, sensitive and selective for the rapid (second-by-second) determination of neurochemicals in the extracellular space of the brain. This technology could have a major impact on basic science studies of neurotransmitter systems involving drug abuse, disease models and behavior. This CEBRA Stage II mechanism is needed, due to the number of technical issues that must be addressed before these techniques can be disseminated to other researchers.

描述(由申请人提供)：这项第二阶段的CEBRA申请涉及开发神经化学芯片微电极，用于神经化学记录大鼠和小鼠的神经递质释放。该项目的长期目标是开发神经化学芯片，用于在自由活动的大鼠和小鼠的中枢神经系统中快速记录谷氨酸、GABA、乙酰胆碱和胆碱。在技术开发中，我们将首先在大鼠和小鼠身上实施和改进神经化学芯片技术。首先，我们计划优化麻醉大鼠和小鼠的记录方法。这将涉及与薄膜技术公司、混合电路公司和克利夫兰医疗设备公司合作开发微电极。仪器开发将与印刷电路板组装公司合作进行。我们将在体外和体内广泛记录麻醉大鼠前额皮质、纹状体和海马区谷氨酸、GABA、胆碱和乙酰胆碱的释放和摄取。有许多微电极、仪器和记录细节必须首先进行优化，才能开发可靠的神经化学芯片。这些微电极记录将与谷氨酸和胆碱的微透析措施进行比较，以尝试并进一步验证该技术。随着这笔拨款的进展，改进和适应的技术将应用于对清醒行为大鼠和小鼠的研究。自由移动的系绳系统将被开发用于清醒大鼠的4通道测量和小鼠的2通道记录。此外，还将开发一种生物遥测系统，以记录完全不受束缚的系统的老鼠。这将有助于1)提高录音的信噪比，2)增加老鼠的行动自由，以及3)监测大量老鼠的可能性。这些研究的主要目标是开发可靠、灵敏和有选择性的神经化学芯片，用于快速(逐秒)测定大脑细胞外空间中的神经化学物质。这项技术可能会对涉及药物滥用、疾病模型和行为的神经递质系统的基础科学研究产生重大影响。由于在将这些技术传播给其他研究人员之前必须解决许多技术问题，因此需要建立CEBRA第二阶段机制。

项目成果

An allosteric modulator of metabotropic glutamate receptors (mGluR₂), (+)-TFMPIP, inhibits restraint stress-induced phasic glutamate release in rat prefrontal cortex.

• DOI: 10.1111/j.1471-4159.2012.07784.x
• 发表时间: 2012-08
• 期刊: Journal of neurochemistry
• 影响因子: 4.7
• 作者: Hascup ER;Hascup KN;Pomerleau F;Huettl P;Hajos-Korcsok E;Kehr J;Gerhardt GA
• 通讯作者: Gerhardt GA

Targeted over-expression of glutamate transporter 1 (GLT-1) reduces ischemic brain injury in a rat model of stroke.

• DOI: 10.1371/journal.pone.0022135
• 发表时间: 2011
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Harvey BK;Airavaara M;Hinzman J;Wires EM;Chiocco MJ;Howard DB;Shen H;Gerhardt G;Hoffer BJ;Wang Y
• 通讯作者: Wang Y

Bidirectional regulation of emotional memory by 5-HT1B receptors involves hippocampal p11.

• DOI: 10.1038/mp.2012.130
• 发表时间: 2013-10
• 期刊: MOLECULAR PSYCHIATRY
• 影响因子: 11
• 作者: Eriksson, T. M.;Alvarsson, A.;Stan, T. L.;Zhang, X.;Hascup, K. N.;Hascup, E. R.;Kehr, J.;Gerhardt, G. A.;Warner-Schmidt, J.;Arango-Lievano, M.;Kaplitt, M. G.;Ogren, S. O.;Greengard, P.;Svenningsson, P.
• 通讯作者: Svenningsson, P.

Rapid microelectrode measurements and the origin and regulation of extracellular glutamate in rat prefrontal cortex.

• DOI: 10.1111/j.1471-4159.2010.07066.x
• 发表时间: 2010-12
• 期刊: Journal of neurochemistry
• 影响因子: 4.7
• 作者: Hascup ER;Hascup KN;Stephens M;Pomerleau F;Huettl P;Gratton A;Gerhardt GA
• 通讯作者: Gerhardt GA

Histological studies of the effects of chronic implantation of ceramic-based microelectrode arrays and microdialysis probes in rat prefrontal cortex.

• DOI: 10.1016/j.brainres.2009.06.084
• 发表时间: 2009-09-29
• 期刊: Brain research
• 影响因子: 2.9
• 作者: Hascup ER;af Bjerkén S;Hascup KN;Pomerleau F;Huettl P;Strömberg I;Gerhardt GA
• 通讯作者: Gerhardt GA