Synaptic organization and plasticity of the input from the basolateral amygdala t

基底外侧杏仁核输入的突触组织和可塑性

• 批准号: 8668572
• 负责人: Alfredo Fontanini
• 金额: $ 31.11万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-03-01 至 2019-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8668572
• 关键词: Address; Affect; Amygdaloid structure; Animals; Area; Behavior Control; Behavioral; Brain; Brain region; Calculi; Cell Nucleus; Cells; Chemosensitization; Complement; Complex; Cues; Data; Dissection; Electric Stimulation; Evoked Potentials; Frequencies; Glutamates; Goals; Grant; In Vitro; Interneurons; Lateral; Learning; Light; Limbic System; Literature; Measures; Mediating; Membrane Potentials; Mental Depression; Methods; Middle Hypothalamus; Neurons; Patch-Clamp Techniques; Pattern; Physiological; Plastics; Prefrontal Cortex; Process; Property; Pyramidal Cells; Rattus; Recruitment Activity; Resolution; Rewards; Role; Series; Shapes; Signal Transduction; Slice; Stimulus; Synapses; Taste Perception; Techniques; Testing; Thalamic structure; Training; Viral; Work; cell type; extracellular; hedonic; hippocampal pyramidal neuron; in vivo; information processing; insight; neural circuit; novel; novel strategies; optogenetics; patch clamp; photoactivation; postsynaptic; public health relevance; research study; response; reward processing; tool

DESCRIPTION (provided by applicant): The gustatory cortex (GC) receives modulatory inputs from multiple regions of the limbic system. Lateral hypothalamus, medial prefrontal cortex, mediodorsal thalamus and basolateral amygdala (BLA) are all known to send projections to GC (Saper 1982; Allen, Saper et al. 1991; Maffei, Haley et al. 2012). Among these inputs, those from the BLA are the ones whose functional significance has been studied the most. Pharmacological and electrophysiological experiments in alert animals have suggested that inputs from BLA are necessary for GC to process information pertaining to the hedonic value of gustatory stimuli (Piette, Baez- Santiago et al. 2012) and the anticipatory value of taste-predictive cues (Samuelsen, Gardner et al. 2012). In addition, plastic changes of the BLA-GC connection have been associated with taste aversion learning (Guzman-Ramos and Bermudez-Rattoni 2012). Despite the abundance of studies investigating the functional role of the BLA-GC connection (Jones, French et al. 1999; Grossman, Fontanini et al. 2008; Guzman-Ramos and Bermudez-Rattoni 2012; Piette, Baez- Santiago et al. 2012; Parkes and Balleine 2013), very little is known on the synaptic organization and plasticity of these inputs. Evidence from intracellular and extracellular recordings in vivo suggests that BLA-GC inputs might exert complex excitatory as well as inhibitory actions (Yamamoto, Azuma et al. 1984; Hanamori 2009; Stone, Maffei et al. 2011), yet no information is available on the synaptic mechanisms underlying these effects. Furthermore, while analysis of BLA evoked potentials in GC provides evidence for learning-related plasticity at this connection (Escobar, Chao et al. 1998; Jones, French et al. 1999; Escobar and Bermudez-Rattoni 2000; Rodriguez-Duran, Castillo et al. 2011), the mechanisms, rules and postsynaptic targets of this plasticity are unknown. Until recently it has been impossible to selectively activate BLA afferents in vitro to finely dissect th GC circuits recruited by amygdalar inputs. The availability of optogenetic tools has however changed the situation (Zhang, Gradinaru et al. 2010; Stuber, Sparta et al. 2011; Yizhar, Fenno et al. 2011; Britt and Bonci 2013; Wang, Kloc et al. 2013), finally allowing us the fundamental questions pertaining to the synaptic organization of amygdalar afferents to GC to be addressed. The experiments proposed here rely on these novel techniques, combined with in vitro whole cell patch clamp recordings, to directly measure the properties of amygdalar synapses onto pyramidal cells and inhibitory interneurons in GC. This methodological approach will be complemented with pharmacological and behavioral manipulations to test the following hypotheses: 1) BLA afferents make direct functional synapses onto different cell types within GC local circuits; 2) Synaptic inputs onto pyramidal neurons and inhibitory interneurons show activity-dependent plasticity; 3) The strength of BLA- GC synapses is affected by hedonic learning. Altogether these experiments will allow us to investigate the synaptic organization of BLA-GC inputs, their plasticity and the changes associated with aversion learning. This framework represents an entirely novel approach to the study of GC inputs in brain slices and promises to provide the first circuit-level description of amygdalar synapses in the gustatory cortex.

描述(申请人提供)：味觉皮质(GC)接受来自边缘系统多个区域的调制输入。外侧下丘脑、内侧前额叶皮质、背侧丘脑和基底外侧杏仁核(BLA)都向GC发出投射(Saper 1982；Allen，Saper等人)。1991年；Maffei，Haley等人。2012年)。在这些输入中，来自BLA的那些输入的功能意义被研究得最多。对警觉动物的药理学和电生理实验表明，来自BLA的输入对于GC处理与味觉刺激的享乐值有关的信息是必要的(Piette，Baez-Santiago等人)。和味觉预测线索的预期价值(Samuelsen，Gardner等人)。2012年)。此外，BLA-GC连接的可塑性变化与味觉厌恶学习有关(Guzman-Ramos和Bermudez-Rattoni 2012)。尽管对BLA-GC连接的功能作用进行了大量的研究(Jones，French等人)。1999年；Grossman，Fontanini等人。2008年；古兹曼-拉莫斯和贝穆德斯-拉托尼2012年；皮埃特，贝兹-圣地亚哥等人。2012；Parkes和Balleine 2013)，对这些输入的突触组织和可塑性知之甚少。来自体内细胞内和细胞外记录的证据表明，BLA-GC输入可能发挥复杂的兴奋和抑制作用(Yamamoto，Azuma等人)。1984年；Hanamori，2009年；Stone，Maffei等人。然而，关于这些效应背后的突触机制，目前还没有任何信息。此外，虽然对GC中BLA诱发电位的分析提供了与学习相关的可塑性在这一联系上的证据(EScott，Chao等人)。1998年；琼斯，弗兰奇等人。1999年；埃斯科瓦尔和贝穆德斯-拉托尼2000年；罗德里格斯-杜兰，卡斯蒂略等人。这种可塑性的机制、规则和突触后靶点尚不清楚。直到最近，人们还不可能在体外选择性地激活BLA传入，以精细地剖析杏仁核传入所招募的GC回路。然而，光遗传工具的可用性改变了这种情况(Zhang，Gradinaru等人。2010年；斯塔伯，斯巴达等人。2011年；伊扎尔、芬诺等人。2011年；Britt和Bonci 2013年；Wang，Kloc等人。2013)，最后允许我们解决与杏仁核GC传入的突触组织有关的基本问题。本文提出的实验依赖于这些新技术，结合体外全细胞膜片钳记录，直接测量杏仁核突触到GC中锥体细胞和抑制性中间神经元的特性。这一方法将辅以药理学和行为操作来检验以下假设：1)BLA传入神经元与GC局部回路中不同类型的细胞直接进行功能性突触；2)向锥体神经元和抑制性中间神经元的突触输入显示出活动依赖的可塑性；3)BLA-GC突触的强度受到享乐学习的影响。总之，这些实验将使我们能够研究BLA-GC输入的突触组织、它们的可塑性以及与厌恶学习相关的变化。这个框架代表了一种全新的方法来研究脑片中的GC输入，并有望提供第一个味觉皮质中杏仁核突触的电路水平描述。