Dendritic dynamics and the perceptual threshold

实验和心理物理学实验已经证实，有意识感知的过程与初级感觉区域中自上而下的信号和自下而上的信息的整合有关。在这里，从其他皮层区域产生的自上而下的信号被认为构成了关于由自下而上流携带的感觉信息的内部表征和/或预测。虽然自上而下的信息的影响可以通过记录神经元的活动来清楚地证明，但本质上，还不知道潜在的机制是什么，也不知道为什么它们如此重要。第5层锥体神经元已经被证明能够在神经元的顶部和底部同时被激活时进行爆炸性放电活动。这很重要，因为携带自上而下信息的轴突到达皮层的第一层，而自下而上的信号到达锥体神经元的较低（体周）区域。因此，有人提出，在这些细胞中，自上而下的信息通过树突棘波与自下而上的信息相联系。这些尖峰依赖于顶端树突中的钙通道。因此，我们提出了基于皮层的感知的“树突假说”：“感知依赖于锥体神经元中树突钙峰的产生，由自下而上和自上而下信号的组合输入。”这个假设的优点是它导致了一个特定的预测，即树突状Ca 2+瞬变应该参与感知过程。这可以使用常规方法进行测试。在这里，我们建议调查这一假设，通过检查周围的“感知阈值”发生的事件，即事件发生后的刺激强度范围从不可检测到可检测。将训练动物以规定的反应行为对触须刺激作出反应，然后将其用作物体感知试验。我们将使用最先进的技术，包括2光子成像和我们实验室开发的光纤成像系统（“潜望镜”系统），测量感知阈值周围树突状细胞钙活性的变化。我们将通过使用防止树突棘波和自上而下信号的光遗传学方法来测试树突棘波在感知过程中的必要性。

Experimental and psychophysical experiments have established that the process of conscious perception is correlated to the integration of top-down signals with bottom-up information in primary sensory areas. Here, top-down signals arising from other cortical areas are thought to constitute internal representations and/or predictions about sensory information that is carried by the bottom-up stream. Although, the influence of top-down information can be clearly demonstrated with recordings of the activity of neurons, per se, it is not yet known what the underlying mechanisms are nor why they are so crucial. Layer 5 pyramidal neurons have been shown to be capable of explosive firing activity when the top and the bottom of the neuron are both simultaneously activated. This is important because axons carrying top-down information arrive in layer 1 of the cortex and bottom-up signals arrive at the lower (perisomatic) regions of the pyramidal neuron. It has been suggested therefore that top-down information is linked to bottom-up information in these cells via dendritic spikes. These spikes depend on calcium channels in the apical dendrite. We therefore propose the 'Dendrite Hypothesis' for cortex-based perception: 'Perception depends on the generation of dendritic calcium spikes in pyramidal neurons by the combined inputs of bottom-up and top-down signals'. This hypothesis has the advantage that it leads to a specific prediction, i.e. that dendritic Ca2+ transients should be involved in the perceptual process. This can be tested using conventional methodologies. Here, we propose to investigate this hypothesis by examining the events that occur around the 'perceptual threshold', i.e. events occurring after a stimulus ranging in intensity from undetectable to detectable. Animals will be trained to respond to whisker stimuli with a defined response behaviour that is then used as the assay for object perception. We will measure changes in dendritic calcium activity around the perceptual threshold using state-of-the-art techniques including 2-photon imaging and a fiberoptic imaging system ('Periscope' system) developed in our laboratory. We will test the necessity for dendritic spiking in process of perception by using optogenetic approaches for preventing dendritic spikes and top-down signals.