GABA Receptors & Pavlovian Conditioning

健忘症是临床环境中GABA能神经传递增强的结果，GABA系统在某些形式的智力迟钝中发挥作用，但GABA受体在明确的学习回路中的确切作用尚未得到很好的表征。压力和性腺激素也影响GABA功能和学习过程，但这些因素在多大程度上汇聚在共同的大脑机制上，我们所知的就更少了。使用具有良好特征的神经回路的学习准备，我们将确定压力和激素环境中的其他变化如何通过GABA受体影响学习。这项工作的一个关键焦点将是激素因素如何通过神经类固醇影响学习和记忆

Amnesia is a consequence of enhancing GABAergic neurotransmission in clinical settings and GABA systems play a role in some forms of mental retardation but the precise role of GABA receptors in well-defined learning circuits is not well characterized. Stress and gonadal hormones also influence GABA function and learning processes but even less is known about the extent to which these factors converge on common brain mechanisms. Using learning preparations that have well characterized neural circuitry we will determine how stress and other alterations in the hormonal milieu act through GABA receptors to influence learning. A key focus of this work will be how hormonal factors impact learning and memory via neurosteroid action at d subunit containing GABA receptors. While d-subunits have limited distribution in the brain, two regions with especially high expression, the dentate gyrus of the hippocampus and granule cells of the cerebellum play a fundamental role in learning and memory. Therefore d subunit containing GABA receptors offer a site at which factors such as stress, can modulate learning systems. Our central hypothesis is that hormonal factors impact learning and memory via neurosteroid action at d subunit containing GABA receptors within the neural circuits mediating specific forms of memory. This hypothesis is based on 4 key findings: 1) Neurosteroids act on dGABARs. 2) dGABARs are strategically placed within well-defined learning/memory circuits. 3) Factors such as stress and estrus cycle influence both hormonal background and learning and memory. 4) d subunit knockout mice are not responsive to neurosteroids. Hormonal variation associated with the estrus cycle will provide one avenue for addressesing these issues. A second will be an animal model of past-traumatic stress disorder, where prior stress enhances certain forms of learning. We seek to determine how both of these factors converge to modulate learning and memory by action an delta containing GABAA receptors.