The role of optogenetic stimulations of parvalbumin-positive interneurons in the prefrontal cortex and the ventral hippocampus on an acute MK-801 model of schizophrenia-like cognitive inflexibility

0570434 - FGÚ 2024 RIV NL eng J - Článek v odborném periodiku
Patrono, Enrico - Hrůzová, Karolína - Svoboda, Jan - Stuchlík, Aleš
The role of optogenetic stimulations of parvalbumin-positive interneurons in the prefrontal cortex and the ventral hippocampus on an acute MK-801 model of schizophrenia-like cognitive inflexibility.
Schizophrenia Research. Roč. 252, February (2023), s. 198-205. ISSN 0920-9964. E-ISSN 1573-2509
Grant CEP: GA ČR(CZ) GF21-16667K; GA MŠMT(CZ) EF19_074/0016409
Institucionální podpora: RVO:67985823
Klíčová slova: MK-801 * attentional set-shifting task * excitatory/inhibitory ratio * gamma waves * theta waves
Obor OECD: Neurosciences (including psychophysiology
Impakt faktor: 4.5, rok: 2022
Způsob publikování: Omezený přístup
https://doi.org/10.1016/j.schres.2022.12.047

Schizophrenia research has increased in recent decades and focused more on its neural basis. Decision-making and cognitive flexibility are the main cognitive functions that are impaired and considered schizophrenia endophenotypes. Cognitive impairment was recently connected with altered functions of N-methyl-d-aspartate (NMDAR) glutamatergic receptors, which increased cortical activity. Selective NMDAR antagonists, such as MK-801, have been used to model cognitive inflexibility in schizophrenia. Decreased GABAergic inhibitory activity has been shown elsewhere with enhanced cortical activity. This imbalance in the excitatory/inhibitory may reduce the entrainment of prefrontal gamma and hippocampal theta rhythms and result in gamma/theta band de-synchronization.The current study established an acute MK-801 administration model of schizophrenia-like cognitive inflexibility in rats and used the attentional set-shifting task in which rats learned to switch/reverse the relevant rule. During the task, we used in vivo optogenetic stimulations of parvalbumin-positive interneurons at specific light pulses in the prefrontal cortex and ventral hippocampus.The first experiments showed that acute dizocilpine in rats produced schizophrenia-like cognitive inflexibility. The second set of experiments demonstrated that specific optogenetic stimulation at specific frequencies of parvalbumin-positive interneurons in the prefrontal cortex and ventral hippocampus rescued the cognitive flexibility rats that received acute MK-801.These findings advance our knowledge of the pivotal role of parvalbumin interneurons in schizophrenia-like cognitive impairment and may guide further research on this severe psychiatric disorder.
Trvalý link: https://hdl.handle.net/11104/0341732