Shang et al. demonstrate that the onset-timing of the axon initial segment (AIS)-GABAergic input, relative to dendritic excitatory glutamatergic inputs, determines its bi-directional regulation of the efficacy of synaptic integration and spike generation in a pyramidal cell. In the cover, trees represent neurons. Flowers represent neuronal spikes induced by the integration of excitatory AIS-specific GABAergic inputs (GPSP_AIS), represented by the left pink arrow, and glutamatergic inputs (EPSP_dend) originating in the dendrites, represented by the right pink arrow. When a GPSP_AIS precedes the EPSP_dend by >10 ms, AIS-GABAergic inputs promote integration efficacy and spike generation, while when they arrive nearly simultaneously, AIS-GABAergic inputs suppress both integration and spiking. Such timing-dependent bi-directional regulatory functions are depicted by different trees with small and blooming blossoms, respectively. See pages 1–13. (Cover provided by Drs Ziwei Shang and Xiaohui Zhang).