Determinants of sparse activity in neocortex

新皮质稀疏活动的决定因素

基本信息

批准号：
10375925
负责人：
ALISON L BARTH
金额：
$ 54.31万
依托单位：
CARNEGIE-MELLON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-02-15 至 2026-11-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10375925
关键词：
Acetylcholine Acute Anatomy Association Learning Aversive Stimulus Brain Cells Coupled Coupling Data Desire for food Detection Disinhibition Environment Epilepsy Feedback Fire - disasters Interneurons Lead Learning Maps Mediating Memory Mental Depression Minor Modeling Molecular Mus Neocortex Neurons Output Parvalbumins Pattern Perception Phase Play Probability Psychological reinforcement Research Rewards Role Runaway Sensory Signal Transduction Skin Slice Somatosensory Cortex Somatostatin Source Stimulus Synapses Synaptic plasticity Tactile Testing Thalamic structure Time Touch sensation Training Vasoactive Intestinal Peptide Vibrissae Water barrel cortex cholinergic cost experience experimental study hippocampal pyramidal neuron in vivo inhibitory neuron learning strategy neocortical optogenetics patch clamp prevent relating to nervous system sensory cortex sensory input

项目摘要

ABSTRACT Synaptic plasticity in neocortical neurons is intimately tied to learning and memory. Decades of research in acute brain slices have characterized the patterns of spike timing required to evoke synaptic change in minute detail, but it remains unknown whether these conditions occur and are sufficient to drive synaptic plasticity in the living brain. Indeed, in vivo recordings indicate that neocortical neurons live in an environment of profound inhibition that lowers overall firing rates and prevents plasticity. How then do cortical neurons escape this inhibition to encounter appropriate conditions for plasticity during learning? New evidence suggests that parvalbumin (PV) GABAergic neurons may play a dominant role in regulating cortical activity and controlling network rewiring, particularly at the early stages of learning. Using a multiwhisker stimulus coupled to a water reward, we have developed a paradigm for sensory association learning that drives rapid changes in excitatory synaptic strength in mouse barrel cortex. Importantly, our new data indicate that PV output to neocortical pyramidal neurons is markedly suppressed at the earliest stages of sensory training. Our experiments will integrate in vivo and acute brain slice recordings to test the hypothesis that PV neurons are a dominant regulator of sensory- evoked activity in mouse barrel cortex. We propose that reward-related acetylcholine release indirectly suppresses PV neural firing to depress PV output and increase sensory-evoked activity during learning. Our experiments will identify mechanisms for cortical disinhibition that facilitate experience-dependent synaptic plasticity in sensory cortex.

抽象的新皮质神经元中的突触可塑性与学习和记忆密切相关。几十年的时间急性脑切片的研究表征了唤起峰值时机的模式分钟细节的突触变化，但是这些情况是否发生，并且足以驱动活大脑中的突触可塑性。确实，体内记录表明新皮层神经元生活在深刻抑制的环境中，可以降低整体射击速率并防止可塑性。那么皮质神经元如何逃脱这种抑制作用学习过程中可塑性的适当条件？新证据表明白蛋白原（PV）GABA能神经元可能在调节皮质活性和控制中起主要作用网络重新布线，特别是在学习的早期阶段。使用多旋风刺激加上水的奖励，我们为感官协会学习了一个范式，驱动小鼠桶皮层中兴奋性突触强度的快速变化。重要的是，我们的新数据表明，在感官训练的最早阶段。我们的实验将整合在体内和急性大脑中切片记录以检验PV神经元是感觉的主要调节剂的假设小鼠桶皮层中的诱发活性。我们提出了与奖励相关的乙酰胆碱释放间接抑制PV神经射击以降低PV输出并增加感官诱发学习过程中的活动。我们的实验将确定皮质抑制的机制促进感觉皮质中的经验依赖性突触可塑性。