Department of Physiology, University of California San Francisco, San Francisco, CA, USA.
Howard Hughes Medical Institute, University of California San Francisco, San Francisco, CA, USA.
Nature. 2020 Jun;582(7813):545-549. doi: 10.1038/s41586-020-2319-4. Epub 2020 May 20.
Animals sense the environment through pathways that link sensory organs to the brain. In the visual system, these feedforward pathways define the classical feedforward receptive field (ffRF), the area in space in which visual stimuli excite a neuron. The visual system also uses visual context-the visual scene surrounding a stimulus-to predict the content of the stimulus, and accordingly, neurons have been identified that are excited by stimuli outside their ffRF. However, the mechanisms that generate excitation to stimuli outside the ffRF are unclear. Here we show that feedback projections onto excitatory neurons in the mouse primary visual cortex generate a second receptive field that is driven by stimuli outside the ffRF. The stimulation of this feedback receptive field (fbRF) elicits responses that are slower and are delayed in comparison with those resulting from the stimulation of the ffRF. These responses are preferentially reduced by anaesthesia and by silencing higher visual areas. Feedback inputs from higher visual areas have scattered receptive fields relative to their putative targets in the primary visual cortex, which enables the generation of the fbRF. Neurons with fbRFs are located in cortical layers that receive strong feedback projections and are absent in the main input layer, which is consistent with a laminar processing hierarchy. The observation that large, uniform stimuli-which cover both the fbRF and the ffRF-suppress these responses indicates that the fbRF and the ffRF are mutually antagonistic. Whereas somatostatin-expressing inhibitory neurons are driven by these large stimuli, inhibitory neurons that express parvalbumin and vasoactive intestinal peptide have mutually antagonistic fbRF and ffRF, similar to excitatory neurons. Feedback projections may therefore enable neurons to use context to estimate information that is missing from the ffRF and to report differences in stimulus features across visual space, regardless of whether excitation occurs inside or outside the ffRF. By complementing the ffRF, the fbRF that we identify here could contribute to predictive processing.
动物通过将感觉器官与大脑连接起来的通路来感知环境。在视觉系统中，这些前馈通路定义了经典的前馈感受野（ffRF），即视觉刺激激发神经元的空间区域。视觉系统还利用视觉上下文——刺激周围的视觉场景——来预测刺激的内容，因此，已经鉴定出一些神经元会被其 ffRF 之外的刺激激发。然而，产生 ffRF 之外的刺激激发的机制尚不清楚。在这里，我们表明，反馈投射到小鼠初级视觉皮层中的兴奋性神经元上，会产生第二个感受野，该感受野由 ffRF 之外的刺激驱动。刺激这个反馈感受野（fbRF）会引发比刺激 ffRF 时更慢且延迟的反应。与刺激 ffRF 相比，这些反应在麻醉和沉默高级视觉区域时会优先减少。来自高级视觉区域的反馈输入相对于其在初级视觉皮层中的假定靶点具有散布的感受野，这使得 fbRF 的产生成为可能。具有 fbRF 的神经元位于接收强烈反馈投射的皮层层中，而不存在于主要输入层中，这与分层处理层次结构一致。观察到大而均匀的刺激——覆盖 fbRF 和 ffRF——会抑制这些反应，表明 fbRF 和 ffRF 是相互拮抗的。虽然表达生长抑素的抑制性神经元被这些大刺激驱动，但表达钙调蛋白结合蛋白 Parvalbumin 和血管活性肠肽的抑制性神经元具有相互拮抗的 fbRF 和 ffRF，类似于兴奋性神经元。因此，反馈投射可能使神经元能够利用上下文来估计 ffRF 中缺失的信息，并报告跨视觉空间的刺激特征差异，而不管兴奋是否发生在 ffRF 内还是 ffRF 外。通过补充 ffRF，我们在这里确定的 fbRF 可能有助于预测处理。
