Intramural Program, National Institute of Mental Health, NIH, Bethesda, MD 20892.
NIH-University of Maryland Graduate Partnerships Program, NIH, Bethesda, MD 20892.
Proc Natl Acad Sci U S A. 2024 Nov 5;121(45):e2318837121. doi: 10.1073/pnas.2318837121. Epub 2024 Nov 1.
The relationship between neurons' input and spiking output is central to brain computation. Studies in vitro and in anesthetized animals suggest that nonlinearities emerge in cells' input-output (IO; activation) functions as network activity increases, yet how neurons transform inputs in vivo has been unclear. Here, we characterize cortical principal neurons' activation functions in awake mice using two-photon optogenetics. We deliver fixed inputs at the soma while neurons' activity varies with sensory stimuli. We find that responses to fixed optogenetic input are nearly unchanged as neurons are excited, reflecting a linear response regime above neurons' resting point. In contrast, responses are dramatically attenuated by suppression. This attenuation is a powerful means to filter inputs arriving to suppressed cells, privileging other inputs arriving to excited neurons. These results have two major implications. First, somatic neural activation functions in vivo accord with the activation functions used in recent machine learning systems. Second, neurons' IO functions can filter sensory inputs-not only do sensory stimuli change neurons' spiking outputs, but these changes also affect responses to input, attenuating responses to some inputs while leaving others unchanged.
神经元输入和脉冲输出之间的关系是大脑计算的核心。在体外和麻醉动物的研究表明，随着网络活动的增加，细胞的输入-输出（IO；激活）函数中会出现非线性，然而，在体内神经元如何转换输入尚不清楚。在这里，我们使用双光子光遗传学来描述清醒小鼠大脑皮层主要神经元的激活功能。我们在神经元的活动随感觉刺激而变化的同时，在胞体上施加固定的输入。我们发现，当神经元被兴奋时，对固定光遗传学输入的反应几乎不变，反映了神经元静息点以上的线性响应状态。相比之下，反应被抑制大大减弱。这种衰减是一种过滤到达抑制细胞的输入的有效手段，优先考虑到达兴奋神经元的其他输入。这些结果有两个主要的含义。首先，体内的躯体神经激活功能与最近的机器学习系统中使用的激活功能一致。其次，神经元的 IO 功能可以过滤感觉输入——感觉刺激不仅改变神经元的脉冲输出，而且这些变化也会影响对输入的反应，减弱对某些输入的反应，而对其他输入则保持不变。
