Fronto-sensory circuit mechanisms of perceptual novelty processing

感知新奇处理的额感觉回路机制

• 批准号: 9430604
• 负责人: Jordan P Hamm
• 金额: $ 12.6万
• 依托单位: COLUMBIA UNIV NEW YORK MORNINGSIDE
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-15 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9430604
• 关键词: 3-Dimensional; Area; Attention; Auditory; Auditory area; Axon; Basic Science; Behavior; Behavioral; Biological; Biological Markers; Biological Models; Brain; Brain region; Calcium; Cells; Cerebral cortex; Clinical Research; Cognition; Cognitive; Cognitive deficits; Correlation Studies; Data; Deltastab; Detection; Dimensions; Disease; Doctor of Philosophy; Electroencephalography; Elements; Environment; Event; Exhibits; Experimental Designs; Functional Magnetic Resonance Imaging; Functional disorder; Future; Goals; Head; Heritability; Human; Ii-Key; Image; Impairment; Individual; Interneurons; Investigation; Label; Laser Scanning Microscopy; Lasers; Learning; Light; Link; Mediating; Mental disorders; Microscopy; Mus; Nature; Neurobiology; Neurons; Neurosciences; Onset of illness; Optics; Parvalbumins; Patients; Pattern; Phase; Population; Positioning Attribute; Postdoctoral Fellow; Prefrontal Cortex; Process; Protocols documentation; Psychotic Disorders; Repetitive Sequence; Research; Rest; Role; Running; Schizophrenia; Sensory; Somatostatin; Stimulus; Support System; Taxonomy; Techniques; Testing; Time; Training; Translating; V1 neuron; Visual; Visual Cortex; Work; Yang; awake; career; cell type; daily functioning; design; deviant; experimental study; flexibility; insight; mouse model; neocortical; novel; novel strategies; novelty processing; optogenetics; preference; programs; relating to nervous system; response; sensory cortex; sensory stimulus; spatiotemporal; therapy development; tool; two-photon

PROJECT SUMMARY Sensory stimuli are naturally perceived within a spatiotemporal and behavioral context, wherein novel events are processed and repetitive elements ignored. Novelty detection is thus cognitive as well as perceptual and is critical for daily function and survival. Studies using “oddball” stimuli demonstrate that psychiatric disorders, including schizophrenia (SZ), involve abnormal sensorineuronal processing of novelty which predicts deficits in cognition and everyday functioning. In his PhD, the candidate characterized the multivariate complexity and heritability of oddball EEG responses to show how they could help build a biological taxonomy of psychosis. Yet a mechanistic understanding of how brain circuits process context, and the pathophysiology underlying patient deficits, is unattainable with human studies alone. As a postdoc, the candidate mastered two-photon calcium imaging (2P-Ca++) and chemicogenetics to develop a mouse model of novelty detection in visual cortical circuits (V1), showing a key role for somatostatin interneurons, a pathophysiologically relevant cell type in SZ. While context processing involves ongoing adaptations within sensory cortex, it also requires information about the past and behavioral goals, which may implicate larger brain networks involving prefrontal cortex (PFC). AIM1 expands the candidates work in V1 to study the mechanisms and nature of PFC’s top-down influence. Experiments will test how direct axonal inputs from PFC actively modify the multicellular circuit dynamics in V1 during in oddball paradigms. To this end, the candidate must learn a state of the art holographic technique using spatial light modulators (SLM) developed in the host lab (NIkolenko et al, 2008; Yang et al 2016) to enable the i) simultaneous observation of layer I (PFC axons) and underlying layer 2-5 (V1 neurons) with fast 3D 2P-Ca++, and ii) holographic optogenetic manipulation of specific circuit elements (e.g. PFC inputs to interneurons) to uncover the causal interactions among three critical neurobiological scales: cells, ensembles, and networks. Patient oddball studies highlight deficits in both passive (automatic) and active (attentional) aspects of novelty processing, which may involve non-overlapping neural pathophysiology. In AIM2, the candidate will uncover the behavioral relevance of this PFC-V1 circuit. Working closely with consultants Drs. Churchland and Gogos, the candidate will learn to design behavioral training protocols in head-fixed mice, eliciting responses to novelty in a dynamic oddball paradigm. Building on findings from in AIM1, the candidate will differentiate attentive from pre-attentive circuit functions and establish when and how context is encoded and used to guide behavior. These studies will yield i) biomechanistic information for interpreting novelty processing deficits in humans and ii) key insights into how emergent activity of the cerebral cortex arises from cellular diversity and interregional connectivity. This work will position the candidate to pursue his career goal of a research program which translates empirical biomarkers of sensory and cognitive deficits to model systems, wherein basic research with cutting edge neuroscience tools can provide promising insights and strategies for novel treatments.

项目概要 感官刺激是在时空和行为背景下自然感知的，因此新颖 因此，事件被处理，重复元素被忽略，新颖性检测既是认知的，也是感知的。 使用“奇怪”刺激的研究表明，这对于日常功能和生存至关重要。 包括精神分裂症 (SZ) 在内的疾病涉及异常的感觉神经元对新奇事物的处理，从而预测 在他的博士学位中，该候选人描述了认知和日常功能的缺陷。 以及奇怪的脑电图反应的遗传性，以展示它们如何帮助建立精神病的生物分类学。 然而，对大脑回路如何处理上下文以及潜在的病理生理学的机械理解 作为一名博士后，该候选人掌握了双光子技术，这是无法单独通过人类研究来实现的。 钙成像 (2P-Ca++) 和化学遗传学开发视觉皮层新颖性检测的小鼠模型 电路 (V1)，显示生长抑素中间神经元的关键作用，生长抑素中间神经元是 SZ 中一种病理生理相关的细胞类型。 虽然上下文处理涉及感觉皮层内的持续适应，但它也需要信息 关于过去和行为目标，这可能意味着涉及前额皮质（PFC）的更大的大脑网络。 AIM1 扩展了 V1 中候选人的工作，以研究 PFC 自上而下影响的机制和性质。 实验将测试 PFC 的直接轴突输入如何主动修改 V1 中的多细胞电路动力学 为此，候选人必须学习使用最先进的全息技术。 主机实验室开发的空间光调制器（SLM）（NIkolenko 等人，2008；Yang 等人，2016） i) 使用快速 3D 2P-Ca++ 同时观察 I 层（PFC 轴突）和底层 2-5 层（V1 神经元）， ii) 对特定电路元件（例如中间神经元的 PFC 输入）进行全息光遗传学操作 揭示三个关键神经生物学尺度之间的因果相互作用：细胞、集合和网络。 患者的奇怪研究强调了被动（自动）和主动（注意力）方面的缺陷 新颖性处理，可能涉及非重叠的神经病理生理学，在 AIM2 中，候选人将。 与顾问 Churchland 和 Drs 密切合作，揭示该 PFC-V1 电路的行为相关性。 Gogos，候选人将学习设计头部固定小鼠的行为训练方案，引发对 基于 AIM1 的发现，候选人将区分注意力。 从前注意回路功能中提取信息，并确定何时以及如何对上下文进行编码并用于指导行为。 这些研究将产生 i) 用于解释人类新奇处理缺陷的生物力学信息 ii）关于大脑皮层的突发活动如何由细胞多样性和区域间产生的关键见解 这项工作将使候选人能够追求他的研究计划的职业目标，该目标 将感觉和认知缺陷的经验生物标志物转化为模型系统，为基础研究提供 尖端的神经科学工具可以为新型治疗提供有前景的见解和策略。

项目成果

Spatiotemporal dynamics across visual cortical laminae support a predictive coding framework for interpreting mismatch responses.

视觉皮层的时空动态支持解释不匹配反应的预测编码框架。

• DOI: 10.1093/cercor/bhad215
• 发表时间: 2023-06-12
• 期刊: Cerebral cortex
• 影响因子: 3.7
• 作者: Connor G. Gallimore;David A Ricci;Jordan P. Hamm
• 通讯作者: Jordan P. Hamm

Robust multisensory deviance detection in the mouse parietal associative area.

小鼠顶叶联想区域的稳健多感觉异常检测。

• 发表时间: 2023-09-25
• 作者: Van Derveer, Alice B;Ross, Jordan M;Hamm, Jordan P
• 通讯作者: Hamm, Jordan P