A mouse line for inducible and reversible silencing of specific neurons

Abstract

Background: Genetic methods for inducibly and reversibly inhibiting neuronal activity of specific neurons are critical for exploring the functions of neuronal circuits. The engineered human glycine receptor, called ivermectin (IVM)-gated silencing receptor (IVMR), has been shown to possess this ability in vitro. Results: Here we generated a mouse line, in which the IVMR coding sequence was inserted into the ROSA26 locus downstream of a loxP-flanked STOP cassette. Specific Cre-mediated IVMR expression was revealed by mis-expression of Cre in the striatum and by crossing with several Cre lines. Behavioral alteration was observed in Rosa26-IVMR mice with unilateral striatal Cre expression after systemic administration of IVM, and it could be re-initiated when IVM was applied again. A dramatic reduction in neuron firing was recorded in IVM-treated free moving Rosa26-IVMR;Emx1-Cre mice, and neuronal excitability was reduced within minutes as shown by recording in brain slice. Conclusion: This Rosa26-IVMR mouse line provides a powerful tool for exploring selective circuit functions in freely behaving mice.