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
Language English Country Netherlands Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
36657364
DOI
10.1016/j.schres.2022.12.047
PII: S0920-9964(22)00494-7
Knihovny.cz E-resources
- Keywords
- Attentional set-shifting task, Excitatory/inhibitory ratio, Gamma waves, MK-801, theta waves,
- MeSH
- Dizocilpine Maleate * pharmacology MeSH
- Hippocampus metabolism MeSH
- Interneurons metabolism MeSH
- Cognition MeSH
- Rats MeSH
- Optogenetics MeSH
- Parvalbumins metabolism MeSH
- Prefrontal Cortex metabolism MeSH
- Receptors, N-Methyl-D-Aspartate metabolism MeSH
- Schizophrenia * MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Dizocilpine Maleate * MeSH
- Parvalbumins MeSH
- Receptors, N-Methyl-D-Aspartate MeSH
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.
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