Journal of International Psychiatry

Objective PVcre/Grin1fl/+ mice line was constructed to selectively knock-down the NMDA receptoer subunits, Grin1, in Parvabumin positive interneurons to model the schizophrenia-like behaviours in animal models, in which to preliminarily explore the effect of iTBS during the developmental period on schizophrenia-like behaviors in the model mice. Methods Eighteen 4-weeks-old PVcre/Grin1fl/+ mice were randomly divided into a sham stimulation group（only feel the vibration of the coil but not receive pulse stimulation）and three experimental group (respectively received treatments with stimulation intensities of 3%, 6%, and 9% of the max output of the TMS equipment).All groups received consecutive treatment in the prefrontal cortex for 10 days. After the treatment, open-field test, novel object recognition test, Y-maze test, elevated O-maze test, forced swimming test and prepulse inhibition test were conducted successively at the age of 7 weeks to evaluate the corresponding behavioral performances of the model mice. Results The Y-maze test revealed a significantly lower recognition index for the model group compared with the control (P < 0.01). The forced swimming test revealed significantly higher freezing time (P < 0.05) and lower swimming distance (P < 0.05) for the model group compared with the controls. After developmental iTBS treatment, the 9% stimulation intensity group exhibited significantly increased ratio of open arm duration (P < 0.05) compared with the sham group in the elevated O maze test. The 9% stimulation intensity group also exhibited significantly reduced freezing time (P < 0.05) compared with the sham group in the forced swimming test. Prepulse inhibition test (79db + 120db) results demonstrated a marginal significant higher inhibition rate of the startle reflex (P < 0.1) in the 9% stimulation intensity group relative to the sham group. Conclusion PVcre/Grin1fl/+ mice line show cognitive deficts and depression-like behaviors; Low-intensity iTBS during the developmental period can partially rescue the anxiety-like, depression-like behaviors and sensorimotor gating deficits in PVcre/Grin1fl/+ model mice.

Schizophrenia; Intermittent theta burst stimulation; Parvalbumin interneuron; N-methyl-D-aspartic acid receptor；Gene knockout