In the neocortex, neuronal processing of sensory events is significantly influenced by context. For instance, responses in sensory cortices are suppressed to repetitive or redundant stimuli, a phenomenon termed “stimulus-specific adaptation” (SSA). However, in a context in which that same stimulus is novel, or deviates from expectations, neuronal responses are augmented. This augmentation is termed “deviance detection” (DD). This contextual modulation of neural responses is fundamental for how the brain efficiently processes the sensory world to guide immediate and future behaviors. Notably, context modulation is deficient in some neuropsychiatric disorders such as schizophrenia (SZ), as quantified by reduced “mismatch negativity” (MMN), an electroencephalography waveform reflecting a combination of SSA and DD in sensory cortex. Although the role of NMDA-receptor function and other neuromodulatory systems on MMN is established, the precise microcircuit mechanisms of MMN and its underlying components, SSA and DD, remain unknown. When coupled with animal models, the development of powerful precision neurotechnologies over the past decade carries significant promise for making new progress into understanding the neurobiology of MMN with previously unreachable spatial resolution. Currently, rodent models represent the best tool for mechanistic study due to the vast genetic tools available. While quantifying human-like MMN waveforms in rodents is not straightforward, the “oddball” paradigms used to study it in humans and its underlying subcomponents (SSA/DD) are highly translatable across species. Here we summarize efforts published so far, with a focus on cortically measured SSA and DD in animals to maintain relevance to the classically measured MMN, which has cortical origins. While mechanistic studies that measure and contrast both components are sparse, we synthesize a potential set of microcircuit mechanisms from the existing rodent, primate, and human literature. While MMN and its subcomponents likely reflect several mechanisms across multiple brain regions, understanding fundamental microcircuit mechanisms is an important step to understand MMN as a whole. We hypothesize that SSA reflects adaptations occurring at synapses along the sensory-thalamocortical pathways, while DD depends on both SSA inherited from afferent inputs and resulting disinhibition of non-adapted neurons arising from the distinct physiology and wiring properties of local interneuronal subpopulations and NMDA-receptor function.

在新皮层中，感觉事件的神经元处理受上下文的影响很大。例如，感觉皮层的反应被抑制为重复或冗余刺激，这种现象被称为“刺激特异性适应”（SSA）。但是，在相同刺激是新颖的或偏离预期的情况下，神经元反应会增强。这种增强被称为“距离检测”（DD）。这种神经反应的上下文调节是大脑如何有效处理感官世界以指导当前和未来行为的基础。值得注意的是，上下文调节在某些神经精神疾病（如精神分裂症（SZ））中是不足的，可以通过减少“失配负性”（MMN）来量化，这种失调是一种脑电图波形，反映了感觉皮层中SSA和DD的组合。尽管已经建立了NMDA受体功能和其他神经调节系统在MMN上的作用，但MMN及其潜在组件SSA和DD的精确微电路机制仍然未知。当与动物模型结合使用时，过去十年来强大的精密神经技术的发展为在以以前无法达到的空间分辨率理解MMN的神经生物学方面取得新进展提供了巨大的希望。当前，由于可用的大量遗传工具，啮齿动物模型代表了机械研究的最佳工具。虽然在啮齿动物中量化类似于人的MMN波形并非易事，但用于在人类及其潜在子组件（SSA / DD）中进行研究的“ oddball”范式在物种间具有很高的转换性。在这里，我们总结到目前为止所发表的努力，着重于动物皮层测量的SSA和DD，以保持与皮层起源的经典测量MMN的相关性。虽然测量和对比这两种成分的机理研究很少，但我们从现有的啮齿动物，灵长类动物和人类文献中合成了一组潜在的微电路机制。虽然MMN及其子组件可能反映了跨多个大脑区域的几种机制，但是了解基本的微电路机制是从整体上理解MMN的重要一步。我们假设SSA反映了沿感觉-丘脑皮质通路突触发生的适应，