Novel Interneurons Mediating Feedforward Inhibition

介导前馈抑制的新型中间神经元

• 批准号: 8656154
• 负责人: ARIEL AGMON
• 金额: $ 31.09万
• 依托单位: WEST VIRGINIA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-01-15 至 2016-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8656154
• 关键词: AMPA Receptors; Action Potentials; Allatostatin; Animals; Area; Auditory; Autistic Disorder; Behavior; Behavioral; Cells; Cerebral cortex; Conscious; Dendrites; Distal; Employee Strikes; Environment; Equilibrium; Evolution; Excitatory Postsynaptic Potentials; Exhibits; Feedback; Fire - disasters; Foundations; Frequencies; Future; Goals; Grant; Human; In Vitro; Interneurons; Kainic Acid Receptors; Kinetics; Knock-out; Knockout Mice; Knowledge; Mediating; Methods; Minority; Molecular; Mouse Strains; Mus; N-Methyl-D-Aspartate Receptors; Neurons; Participant; Parvalbumins; Pattern; Perception; Pharmacogenetics; Play; Population; Population Heterogeneity; Presynaptic Terminals; Process; Property; Role; Schizophrenia; Sensory; Sensory Process; Shapes; Somatostatin; Stimulus; Synapses; Testing; Thalamic structure; Time; TimeLine; Training; Transgenic Mice; Transgenic Organisms; Visual; Wakefulness; Work; awake; barrel cortex; base; desensitization; excitatory neuron; experience; gamma-Aminobutyric Acid; in vivo; inhibitory neuron; innovation; neglect; neuronal cell body; neuronal patterning; novel; public health relevance; receptive field; receptor; research study; response; somatosensory; spatiotemporal; stellate cell; synaptic inhibition

DESCRIPTION (provided by applicant): All incoming auditory, visual and somatosensory information is relayed through the thalamus to the cerebral cortex, which, during wakefulness, is responsible for transforming these sensory inputs into a spatio-temporal pattern of neuronal activity that gives rise to an internal representation of the external world. These representations are a crucial component of our conscious experience. Understanding how incoming information from the thalamus gives rise to cortical activity is therefore essential for understanding both normal and pathological states of consciousness, such as schizophrenia or autism, when internal representations appear to go awry. Although they are only a minority of all cortical neurons, GABA-releasing inhibitory interneurons play a crucial role in these transformations. By providing both feedforward and feedback inhibition, inhibitory interneurons restrict electrical activity in the majority excitatory neurons to a precisely tuned response in time and in space. Therefore, understanding how sensory representations are generated requires a detailed knowledge of the identity and properties of the GABAergic neurons and synapses which mediate feedforward and feedback inhibition, and of their responses to incoming sensory information, but such knowledge is still lacking. The two largest and best studied inhibitory subtypes are "fast spiking" interneurons and somatostatin-containing interneurons. Previous studies suggested that feedforward inhibition is mediated exclusively by fast-spiking cells. In contrast, we showed in the previous grant period that both subtypes of interneurons mediate feedforward inhibition, but do so under very different stimulation regimes: fast- spiking interneurons will fire in response to a transient stimulus, while somatostatin- containing interneurons will fire in response to a sustained input. During the current grant period, we will use electrophysiological and pharmacological methods to elucidate the biophysical basis for these striking differences in response properties, and we will use novel genetically modified strains of mice to test the roles of each interneuron subtype in shaping responses of cortical neurons to incoming sensory information from the thalamus.

描述（由申请人提供）：所有传入的听觉、视觉和体感信息都通过丘脑传递到大脑皮层，在清醒期间，大脑皮层负责将这些感觉输入转化为神经元活动的时空模式，从而产生外部世界的内部表征。这些表征是我们意识体验的重要组成部分。因此，了解来自丘脑的传入信息如何引起皮质活动对于理解正常和病理的意识状态（例如精神分裂症或自闭症）（当内部表征似乎出现问题时）至关重要。尽管它们只占所有皮质神经元的一小部分，但释放 GABA 的抑制性中间神经元在这些转变中发挥着至关重要的作用。通过提供前馈和反馈抑制，抑制性中间神经元将大多数兴奋性神经元的电活动限制在时间和空间上精确调整的响应。因此，了解感觉表征是如何生成的，需要详细了解介导前馈和反馈抑制的 GABA 能神经元和突触的身份和特性，以及它们对传入感觉信息的反应，但目前仍然缺乏这些知识。两种最大且研究最充分的抑制亚型是“快速尖峰”中间神经元和含有生长抑素的中间神经元。先前的研究表明，前馈抑制仅由快速尖峰细胞介导。相比之下，我们在之前的资助期间表明，两种亚型的中间神经元都介导前馈抑制，但在非常不同的刺激方案下这样做：快速放电的中间神经元将响应瞬时刺激而放电，而含有生长抑素的中间神经元将响应持续的输入而放电。在当前的资助期内，我们将使用电生理学和药理学方法来阐明这些反应特性显着差异的生物物理基础，并且我们将使用新型转基因小鼠品系来测试每种中间神经元亚型在塑造皮质神经元对来自丘脑的传入感觉信息的反应中的作用。

项目成果

A novel, jitter-based method for detecting and measuring spike synchrony and quantifying temporal firing precision.

• DOI: 10.1186/2042-1001-2-5
• 发表时间: 2012-05-02
• 期刊: Neural systems & circuits
• 作者: Agmon A

Differential Excitation of Distally versus Proximally Targeting Cortical Interneurons by Unitary Thalamocortical Bursts.

单一丘脑皮质爆发对远端和近端靶向皮质中间神经元的差异激发。

• DOI: 10.1523/jneurosci.0739-16.2016
• 发表时间: 2016
• 期刊: The Journal of neuroscience : the official journal of the Society for Neuroscience
• 作者: Hu,Hang;Agmon,Ariel
• 通讯作者: Agmon,Ariel