Department of Psychiatry, University of Calgary, Calgary, AB, Canada.
Hotchkiss Brain Institute & The Mathison Centre for Mental Health Research and Education, University of Calgary, Calgary, AB, Canada.
Transl Psychiatry. 2020 Jan 21;10(1):20. doi: 10.1038/s41398-020-0713-1.
Medically unexplained symptoms in depression are common. These individual-specific complaints are often considered an 'idiom of distress', yet animal studies suggest that cortical sensory representations are flexible and influenced by spontaneous cortical activity. We hypothesized that stress would reveal activity dynamics in somatosensory cortex resulting in greater sensory-evoked response variability. Using millisecond resolution in vivo voltage sensitive dye (VSD) imaging in mouse neocortex, we characterized spontaneous regional depolarizations within limb and barrel regions of somatosensory cortex, or spontaneous sensory motifs, and their influence on sensory variability. Stress revealed an idiosyncratic increase in spontaneous sensory motifs that is normalized by selective serotonin reuptake inhibitor treatment. Spontaneous motif frequency is associated with increased variability in sensory-evoked responses, and we optogenetically demonstrate that regional depolarization in somatosensory cortex increases sensory-evoked variability for seconds. This reveals a putative circuit level target for changes in sensory processing and for unexplained physical complaints in stress-related psychopathology.
抑郁症中存在许多无法用医学解释的症状。这些个体特异性的主诉通常被认为是“痛苦的表达”，但动物研究表明，皮质感觉代表具有灵活性，并受到自发皮质活动的影响。我们假设，压力会揭示躯体感觉皮层中的活动动态，从而导致更大的感觉诱发反应可变性。我们使用小鼠新皮层中的毫微秒分辨率的电压敏感染料（VSD）成像，对躯体感觉皮层的肢体和桶状皮层内的自发区域去极化，或自发感觉模式，以及它们对感觉可变性的影响进行了描述。压力揭示了自发感觉模式的特异性增加，而选择性 5-羟色胺再摄取抑制剂治疗可使其正常化。自发模式频率与感觉诱发反应的可变性增加有关，我们通过光遗传学证明，躯体感觉皮层的区域去极化可使感觉诱发的可变性增加数秒。这揭示了一种潜在的与感觉处理变化以及与压力相关的精神病理学中无法解释的身体主诉有关的回路水平靶点。
