Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA.
Neurosurgery Department, Stanford University School of Medicine, Stanford, CA 94305, USA.
Neuron. 2018 Jul 11;99(1):147-162.e8. doi: 10.1016/j.neuron.2018.05.025. Epub 2018 Jun 14.
The mammalian hippocampus forms a cognitive map using neurons that fire according to an animal's position ("place cells") and many other behavioral and cognitive variables. The responses of these neurons are shaped by their presynaptic inputs and the nature of their postsynaptic integration. In CA1 pyramidal neurons, spatial responses in vivo exhibit a strikingly supralinear dependence on baseline membrane potential. The biophysical mechanisms underlying this nonlinear cellular computation are unknown. Here, through a combination of in vitro, in vivo, and in silico approaches, we show that persistent sodium current mediates the strong membrane potential dependence of place cell activity. This current operates at membrane potentials below the action potential threshold and over seconds-long timescales, mediating a powerful and rapidly reversible amplification of synaptic responses, which drives place cell firing. Thus, we identify a biophysical mechanism that shapes the coding properties of neurons composing the hippocampal cognitive map.
哺乳动物的海马体利用根据动物位置（“位置细胞”）和许多其他行为和认知变量发射的神经元形成认知图。这些神经元的反应受到其突触前输入和突触后整合的性质的影响。在 CA1 锥体神经元中，体内的空间反应表现出对基线膜电位的惊人超线性依赖性。这种非线性细胞计算的生物物理机制尚不清楚。在这里，我们通过结合体外、体内和计算方法，表明持续的钠电流介导了位置细胞活动对膜电位的强烈依赖性。这种电流在动作电位阈值以下的膜电位下运作，并在数秒长的时间尺度上运作，介导了对突触反应的强大而快速的可逆放大，从而驱动位置细胞的发射。因此，我们确定了一种生物物理机制，它塑造了构成海马体认知图的神经元的编码特性。
