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Specific parvalbumin-positive optogenetic stimulations in specific brain regions restore navigational flexibility in an acute MK801 mouse model of schizophrenia

E. Patrono, D. Černotová, J. Svoboda, A. Stuchlík

. 2025 ; 585 (-) : 85-96. [pub] 20250902

Jazyk angličtina Země Spojené státy americké

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc25021393

Impairments in decision-making and behavioral flexibility in patients with schizophrenia (SCZ) are currently among the most investigated aspects of SCZ. Increased GLUergic excitatory activity and decreased GABAergic inhibitory activity induce mPFC-vHPC γ/θ band desynchronization in many tasks where behavioral flexibility is tested. However, these tasks used "perceptual" decision-making/flexibility but not navigational decision-making/flexibility. Our study investigated the role of frequency-specific optogenetic stimulation of GABAergic parvalbumin-positive (PV+) interneurons in two pivotal brain structures used in flexibility (mPFC) and navigation (vHPC), at frequencies resembling the γ/θ band (50 Hz, γ-like; and 10 Hz, θ-like) in an acute MK801 mouse model of navigational inflexibility. We used a modified version of the active place avoidance task on a rotating arena. The behavioral results revealed that frequency-specific optogenetic stimulation of the mPFC or vHPC had different effects on restoring navigational flexibility. Moreover, immunohistochemical assays confirmed that optogenetic stimulations activated PV+ interneurons that were transfected with the optogenetic actuators, advancing our understanding of the pivotal role of PV+ activity in SCZ-like navigational decision-making/flexibility.

Citace poskytuje Crossref.org

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