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Key points: The neuronal and network properties that persist during an isoelectric coma remain largely unknown. We developed a new in vivo rat model to assess cell excitability and sensory responsiveness in the thalamo‐cortical pathway during an isoflurane‐induced isoelectric brain state. The isoelectric electrocorticogram reflected a complete interruption of spontaneous synaptic and firing activities in cortical and thalamic neurons. Cell excitability and sensory responses in the thalamo‐cortical network persisted at a reduced level in the isoelectric condition and returned to control values after resumption of background brain activity. These findings could lead to a reassessment of the functional status of the drug‐induced isoelectric state: a latent state in which individual neurons and networks retain to some extent the ability of being activated by external inputs. The neuronal and network properties that persist in an isoelectric brain completely deprived of spontaneous electrical activity remain largely unexplored. Here, we developed a new in vivo rat model to examine cell excitability and sensory responsiveness in somatosensory thalamo‐cortical networks during the interruption of endogenous brain activity induced by high doses of isoflurane. Electrocorticograms (ECoGs) from the barrel cortex were captured simultaneously with either intracellular recordings of subjacent cortical pyramidal neurons or extracellular records of the related thalamo‐cortical neurons. Isoelectric ECoG periods reflected the disappearance of spontaneous synaptic and firing activities in cortical and thalamic neurons. This was associated with a sustained membrane hyperpolarization and a reduced intrinsic excitability in deep‐layer cortical neurons, without significant changes in their membrane input resistance. Concomitantly, we found that whisker‐evoked potentials in the ECoG and synaptic responses in cortical neurons were attenuated in amplitude and increased in latency. Impaired responsiveness in the barrel cortex paralleled with a lowering of the sensory‐induced firing in thalamic cells. The return of endogenous brain electrical activities, after reinstatement of a control isoflurane concentration, led to the recovery of cortical neurons excitability and sensory responsiveness. These findings demonstrate the persistence of a certain level of cell excitability and sensory integration in the isoelectric state and the full recovery of cortico‐thalamic functions after restoration of internal cerebral activities. Key points: The neuronal and network properties that persist during an isoelectric coma remain largely unknown. We developed a new in vivo rat model to assess cell excitability and sensory responsiveness in the thalamo‐cortical pathway during an isoflurane‐induced isoelectric brain state. The isoelectric electrocorticogram reflected a complete interruption of spontaneous synaptic and firing activities in cortical and thalamic neurons. Cell excitability and sensory responses in the thalamo‐cortical network persisted at a reduced level in the isoelectric condition and returned to control values after resumption of background brain activity. These findings could lead to a reassessment of the functional status of the drug‐induced isoelectric state: a latent state in which individual neurons and networks retain to some extent the ability of being activated by external inputs. [ABSTRACT FROM AUTHOR]