in the central nervous system (cnS), γ-aminobutyric acid A (GABA A ) receptors mediate two types of inhibitory effects. Phasic inhibition involves the activation of synaptic GABA A receptors, and tonic inhibition is mediated by extrasynaptic GABA A receptors. GABA A receptors are important regulators of neuronal activity and are involved in a range of neurological disorders. In this study, we conducted sIPSCs recordings on hippocampal CA1 pyramidal neurons in WT SD rats and found that exposure to blue light could specifically block the tonic inhibition and sIPSCs, and regulate neuronal activity. These observations indicate the existence of a non-opsin photosensitive pathway that regulates the GABA inhibitory system in the CNS.In the human brain, the principal inhibitory system acts via GABA A and GABA B receptors. GABA A receptors mediate two types of inhibition. One is phasic inhibition, which involves activation of the synaptic αβγ GABA receptor subunit assembly, by transient high concentrations of GABA, whereas the second inhibition is tonic inhibition, which depends on the continuous activation of extrasynaptic high affinity GABA A receptors, that include α4, α5, α6, and δ subunits 1,2 . Synaptic GABA A are extensively expressed throughout the brain. Extrasynaptic GABA A receptors are widely expressed in cerebellar granule cells 3 , neocortex 4 , thalamus 5 , the striatum 6 , hypothalamus 7 , and hippocampus 8 .The balance of excitation and inhibition (E:I) is fundamental for normal brain function. Dysfunction in the GABA inhibitory system is associated with several neurological disorders, such as depression, stress, and epilepsy. Detailed investigation of the GABA inhibitory system in research primarily depends on the use of GABA receptor antagonists or optogenetic methods. A recent study reported that the activity of fast-spiking interneurons in the cerebral cortex could be suppressed by heat produced by sustained light exposure with a power of 3 mW~15 mW, which is commonly used in optogenetic procedures. However, this phenomenon was not observed in the hippocampal CA1 area 9 .In this study, we found that blue light could specifically and reversibly block tonic inhibition and sIPSCs in hippocampal CA1 pyramidal neurons in 6-to 8-week-old female WT SD rats. This effect was unrelated to the heating effect, which indicated the existence of a non-opsin photosensitive pathway that regulates the GABA inhibitory system. open