Neuronal spiking in the mammalian forebrain is dominated by a heterogeneous ground state

• Neurons have a ground state mode of irregular spiking at cell-specific rates • Activated states are more regular, faster spiking patterns specific to each region • Most spikes occur in the low-rate ground state mode • Balanced network models reproduce both ground and activated spiking modes Neurons have a ground state mode of irregular spiking at cell-specific rates Activated states are more regular, faster spiking patterns specific to each region Most spikes occur in the low-rate ground state mode Balanced network models reproduce both ground and activated spiking modes Neuronal firing patterns have significant spatiotemporal variability with no agreed-upon theoretical framework. Using a combined experimental and modeling approach, we found that spike interval statistics of excitatory neurons in the mammalian forebrain are dominated by a universal low-rate (“ground state”; GS) mode, with irregular spiking at neuron-specific rates. In contrast, when firing rates are increased during intrinsic network patterns or in response to stimuli, spiking across neurons is temporally coordinated with more regular spiking patterns in a region- and brain-state-specific manner. We demonstrate the generality of this distinction in six forebrain areas and show that the majority of spikes in all regions are emitted in the GS mode, emphasizing its physiological importance. We hypothesize that GS spiking maintains persistent neuronal dynamics.