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（由申请人提供）：味觉皮层（GC）接收来自边缘系统多个区域的调节输入。众所周知，下丘脑，内侧前额叶皮质，中齿丘脑和基底外侧杏仁核（BLA）都将投影发送给GC（Saper 1982; Allen，Saper等，1991; Maffei，Maffei，Haley，Haley et etal。2012）。在这些输入中，来自BLA的输入是最重要的功能意义的输入。警报动物中的药理和电生理实验表明，BLA的投入是GC处理与味觉刺激的享乐值有关的信息（Piette，Baez-Santiago etal。2012）和味觉预测性线索的预期价值（Samuelsen，Gardner等。2012年）。此外，BLA-GC连接的塑性变化与口味厌恶学习有关（Guzman-Ramos和Bermudez-Rattoni 2012）。 尽管大量研究了BLA-GC连接的功能作用（Jones，French等，1999; Grossman，Fontanini etal。2008; Guzman-Ramos和Bermudez-Rattoni 2012; Piette，Baez-Santiago等人2012; Parkes and Balleine and Balleine 2013; Parkes and Balleine 2013; Parkes and Balleine 2013;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性以及抑制作用（Yamamoto，Azuma等，1984; Hanamori 2009; Hanamori 2009; Stone，Maffei etal。2011）尚未获得这些突触机构的信息，这些机构在这些突触机构上均无到信息。此外，在GC中对BLA诱发潜力的分析提供了与学习相关的可塑性的证据（Escobar，Chao等，1998; Jones，Jones，French etal。1999; Escobar and Bermudez-Rattoni 2000; Rodriguez-Duran，Rodriguez-Duran，Castillo等人，Castillo etal。2011），规则和后的塑料是塑料的。 直到最近，不可能在体外选择性地激活BLA传入，以细化杏仁核输入募集的GC电路。 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.此处提出的实验依赖于这些新技术，并结合了体外全细胞贴片夹记录，以直接测量杏仁核突触到金字塔细胞上的特性和GC中抑制性神经元的抑制性中间神经元。这种方法学方法将与药理和行为操作相辅相成，以检验以下假设：1）BLA传入将直接功能性突触在GC局部电路内的不同细胞类型上进行。 2）对锥体神经元和抑制​​性神经元的突触输入显示活性依赖性可塑性； 3）Bla-GC突触的强度受享乐学习的影响。 这些实验总之将使我们能够研究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。该框架代表了研究大脑切片中GC输入的一种完全新颖的方法，并有望提供阵阵皮层中杏仁核突触的第一个电路级描述。