NOVEL INTERNEURONS MEDIATING FEEDFORWARD THALAMOCORTICAL INHIBITION

介导前向丘脑皮质抑制的新型中间神经元

• 批准号: 7340115
• 负责人: ARIEL AGMON
• 金额: $ 25.64万
• 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 2009-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7340115
• 关键词: Animals; Area; Auditory; Axon; Behavioral; Cells; Cerebral cortex; Chromosome Pairing; Conscious; Dendrites; Depressed mood; Development; Distal; Elements; Environment; Evolution; Figs - dietary; Frequencies; Future; Green Fluorescent Proteins; Hand; Inhibitory Synapse; Interneurons; Kinetics; Label; Leg; Mediating; Minority; Modeling; Morphology; Mus; N-Methyl-D-Aspartate Receptors; Neocortex; Neurons; Participant; Parvalbumins; Pattern; Perception; Pharmacology; Physiological; Physiology; Property; Range; Reporting; Research Personnel; Role; Sensory; Sensory Process; Slice; Somatostatin; Synapses; System; Testing; Tetracycline; Thalamic structure; Thinking; Time; Training; Transgenic Mice; Triad Acrylic Resin; Visual; base; excitatory neuron; experience; follow-up; hippocampal pyramidal neuron; innovation; neural circuit; novel; postsynaptic; programs; quantum; receptor; research study; response; selenophene-6; somatosensory; spatiotemporal; voltage clamp

DESCRIPTION (provided by applicant): Almost everything we know about the world is relayed to layer 4 of our neocortex by the thalamus, via the thalamocortical synapse. The neocortex is responsible for transforming these sensory inputs into the conscious experience we call perception; understanding these transformations is therefore essential for understanding both normal and pathological states of consciousness. GABA-releasing inhibitory interneurons are vital participants in these transformations. In primary sensory cortical areas, thalamocortical inputs strongly activate inhibitory interneurons, which in turn provide disynaptic inhibition to neighboring excitatory neurons. This "feedforward" inhibition holds the cortical response under a powerful but dynamically modulated control, and transforms sensory inputs into spatiotemporal activity patterns. The two largest and best studied GABAergic subtypes are parvalbumin-expressing (PV+), which are "fast spiking" (FS) interneurons, and somatostatin-expressing (SOM+) interneurons. Currently, feedforward thalamocortical inhibition is thought to be mediated solely by PV+, FS interneurons; however, this "one interneuron fits all" model is difficult to reconcile with the need to adjust cortical responses to different behavioral states. Indeed, our preliminary results indicate that, contrary to previous reports, both PV+ and SOM+ interneurons receive direct thalamocortical excitation, albeit with very different temporal dynamics. Our central hypothesis is therefore that both PV+ and SOM+ interneurons mediate feedforward thalamocortical inhibition, but with markedly different spatial and temporal properties, and are therefore likely to contribute differentially to thalamocortical transformations, possibly participating in different behavioral states. To test this hypothesis, we will use novel transgenic mice which we have generated, and in which layer 4 SOM+ interneurons express Green Fluorescent Protein. The hypothesis will be tested by recording electrophysiologically synaptic responses corresponding to the three legs of the thalamocortical "triad" - thalamocortical inputs onto inhibitory interneurons, inhibitory inputs onto layer 4 excitatory neurons, and thalamocortical inputs onto layer 4 excitatory neurons. The results of the proposed study will advance our understanding of the neuronal elements and synaptic circuits that mediate sensory perception, and how they operate during normal and abnormal behavioral states.

描述（由申请人提供）：几乎我们对世界的所有了解都是通过丘脑传递到我们新皮层的第四层，通过丘脑皮层突触。新皮层负责将这些感觉输入转化为我们称之为知觉的意识体验;因此，理解这些转化对于理解意识的正常和病理状态至关重要。释放GABA的抑制性中间神经元是这些转化的重要参与者。在初级感觉皮质区，丘脑皮质的输入强烈激活抑制性中间神经元，这反过来又提供了双突触抑制相邻的兴奋性神经元。这种“前馈”抑制在一个强大但动态调制的控制下保持皮层反应，并将感觉输入转换为时空活动模式。两种最大和研究最好的GABA能亚型是小清蛋白表达（PV+）和生长抑素表达（SOM+）中间神经元，所述小清蛋白表达（PV+）是“快速尖峰”（FS）中间神经元。目前，前馈丘脑皮层抑制被认为是唯一介导的PV+，FS中间神经元，然而，这种“一个中间神经元适合所有”的模型是难以调和的需要，以调整皮层反应不同的行为状态。事实上，我们的初步研究结果表明，与以前的报告相反，PV+和SOM+中间神经元直接接受丘脑皮层兴奋，尽管具有非常不同的时间动态。因此，我们的中心假设是，PV+和SOM+中间神经元介导前馈丘脑皮层抑制，但具有显着不同的空间和时间特性，因此可能有助于差异丘脑皮层的转换，可能参与不同的行为状态。为了验证这一假设，我们将使用我们已经产生的新型转基因小鼠，其中第4层SOM+中间神经元表达绿色荧光蛋白。将通过记录对应于丘脑皮质“三联体”的三条腿的电生理突触反应来测试该假设-丘脑皮质输入到抑制性中间神经元、抑制性输入到第4层兴奋性神经元和丘脑皮质输入到第4层兴奋性神经元。这项研究的结果将促进我们对介导感觉知觉的神经元和突触回路的理解，以及它们在正常和异常行为状态下如何运作。