Correlation between desynchrony of hippocampal neural activity and hyperlocomotion in the model mice of schizophrenia and therapeutic effects of aripiprazole

CNS Neuroscience & Therapeutics, Journal Year: 2024, Volume and Issue: 30(5)

Published: May 1, 2024

Abstract Aims The hippocampus has been reported to be morphologically and neurochemically altered in schizophrenia (SZ). Hyperlocomotion is a characteristic SZ‐associated behavioral phenotype, which associated with dysregulated dopamine system function induced by hippocampal hyperactivity. However, the neural mechanism of underlying hyperlocomotion remains largely unclear. Methods Mouse pups were injected N ‐methyl‐ D ‐aspartate receptor antagonist (MK‐801) or vehicle twice daily on postnatal days (PND) 7–11. In adulthood phase, one cohort mice underwent electrode implantation field CA1 for recording local potentials spike activity. A separate surgery allow calcium imaging while monitoring locomotion. Lastly, effects atypical antipsychotic (aripiprazole, ARI) evaluated Results We found that theta oscillations enhanced MK‐801‐treated mice, but correlation coefficient between spiking activity oscillation was reduced. Consistently, although rate amplitude transients neurons increased, their synchrony locomotion speed disrupted. ARI ameliorated perturbations produced MK‐801 treatment. Conclusions These results suggest disruption coordination may underly neuropathological SZ.

Language: Английский

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Prolonged anesthesia alters brain synaptic architecture

Proceedings of the National Academy of Sciences, Journal Year: 2021, Volume and Issue: 118(7)

Published: Feb. 10, 2021

Significance In human patients, prolonged medically induced coma (pMIC) is associated with significant cognitive deficits. Yet, a synapse-level neuromorphological correlate has been demonstrated experimentally only in early life, when the brain highly plastic. The current notion that synapses become increasingly stabilized and MIC no effect on synaptic dynamics adulthood. longest experimental study of MIC-associated changes ∼6 h. We established pMIC protocol mice found alters architecture object recognition at all ages. Our results ring an alarm bell to medical community call for development individually tailored anesthetic regimens intensified research adjuvant therapeutic strategies maintain structure function during pMIC.

Language: Английский

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Network instability dynamics drive a transient bursting period in the developing hippocampus in vivo

eLife, Journal Year: 2022, Volume and Issue: 11

Published: Dec. 19, 2022

Spontaneous correlated activity is a universal hallmark of immature neural circuits. However, the cellular dynamics and intrinsic mechanisms underlying network burstiness in intact developing brain are largely unknown. Here, we use two-photon Ca

Language: Английский

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Mitochondrial dysfunction following repeated administration of alprazolam causes attenuation of hippocampus-dependent memory consolidation in mice

Aging, Journal Year: 2023, Volume and Issue: 15(19), P. 10428 - 10452

Published: Oct. 5, 2023

The frequently repeated administration of alprazolam (Alp), a highly effective benzodiazepine sedative-hypnotic agent, in anxiety, insomnia, and other diseases is closely related to many negative adverse reactions that are mainly manifested as memory impairment. However, the exact molecular mechanisms underlying these events poorly understood. Therefore, we conducted proteomic analysis on hippocampus mice received Alp for 24 days. A total 439 significantly differentially expressed proteins (DEPs) were identified with compared control group, GO KEGG revealed enrichment terms mitochondrial function, cycle, mitophagy cognition. In vitro experiments have shown may affect cell reduce membrane potential (MMP) induce apoptosis HT22 cells, progress energy metabolism morphology hippocampal neurons. Furthermore, vivo behavioral including IntelliCage System (ICS) nover object recognition (NOR), neuronal pathological changes HE staining, expression levels brain-deprived neuron factor (BDNF) immunohistochemistry showed significant decrease consolidation Alp, which could be rescued by co-administration protector NSI-189. To best our knowledge, this first study identify link between dysfunction impairment directly causes attenuation mice.

Language: Английский

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Calcium Imaging and Electrophysiology of hippocampal Activity under Anesthesia and natural Sleep in Mice

Scientific Data, Journal Year: 2022, Volume and Issue: 9(1)

Published: March 29, 2022

Abstract The acute effects of anesthesia and their underlying mechanisms are still not fully understood. Thus, comprehensive analysis efficient generalization require description in various brain regions. Here we describe a large-scale, annotated collection 2-photon calcium imaging data multi-electrode, extracellular electrophysiological recordings CA1 the murine hippocampus under three distinct anesthetics (Isoflurane, Ketamine/Xylazine Medetomidine/Midazolam/Fentanyl), during natural sleep, wakefulness. We cover several aspects quality standardization provide set tools for autonomous validation, along with workflows reuse exploration. datasets described here capture neural activity hundreds pyramidal cells at single cell resolution. In addition to relevance basic biological research, dataset may find utility computational neuroscience as benchmark models sleep.

Language: Английский

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