Biology subjects

Koketsu, S.

Publications and source records attributed to Koketsu, S..

3 recordsLinked to original sources

bioRxiv2025

Housing environment bilaterally alters transcriptomic profile in the rat hippocampal CA1 region

Brain asymmetry is a fundamental feature of neural organization. However, the molecular basis of hippocampal lateralization in response to environmental stimuli remains poorly understood. Here, we examined the transcriptomic profiles of the left and right hippocampal CA1 regions in rats reared under isolated or enriched housing conditions to elucidate hemisphere-specific responses and shared molecular adaptations. RNA-sequencing analysis revealed lateralized differences in the number and identity of differentially expressed genes, accompanied by distinct biological themes, as indicated by overrepresentation and gene set enrichment analysis. The left CA1 region was prominently engaged in pathways related to synaptic organization and mitochondrial function, whereas the right CA1 region exhibited enrichment in transcriptional regulation and RNA metabolic processes. Despite these asymmetries, co-expression and protein-protein interaction network analyses revealed shared molecular architectures. Immediate early genes formed consistent central hubs across both hemispheres, and a common Mecp2-Grin2b-Cdkl5-Tet3 protein interaction cluster was identified as a potential integrative regulatory module. Additional enrichment analysis of differentially expressed genes shared between hemispheres further highlighted conserved responses, particularly in synaptic plasticity and cell-cell communication. Together, these findings demonstrate that the left and right CA1 regions employ distinct yet partially convergent transcriptional programs to adapt to environmental stimuli. This coordinated molecular asymmetry provides novel insights into hippocampal lateralization and its role in experience-dependent brain plasticity.

neuroscience↗

bioRxiv2023

The defects of the hippocampal ripples and theta rhythm in depression, and the effects of physical exercise on their amelioration.

Accumulated evidence demonstrate that environmental stress affects the hippocampus, functioning in cognition and sociality, and causes various depressive symptoms. In addition, recent findings showed that environmental stress influenced the hippocampal activity correlated with neuroinflammation, and impaired the hippocampal sharp wave ripples (SWRs), pattens of spike sequences, and the theta rhythms, a strong oscillation observed in the hippocampus. The involvement of the electrophysiological alterations in the etiology of depression has not been appreciated especially in the hippocampus. Furthermore, the pathological markers associated with such alterations have not been identified. In the present study, therefore, the impairment of the SWRs and the theta rhythms in the hippocampus of the restraint stress-induced depression model of mice was analyzed. In the model mice the hippocampal SWRs and theta rhythms were impaired in depression, while physical exercise significantly reverted them. As previously reported, chronic stress induced inflammation in the affected hippocampus in parallel with defects of adult neurogenesis, on the other hand physical exercise ameliorated those pathological conditions of the bran in depression. In conclusion, this study demonstrated the implications of impairment of the hippocampal SWRs and theta rhythms in the etiology of depression and their usefulness as diagnostic markers of depression.

neuroscience↗

bioRxiv2020

Brain state-dependent cortico-hippocampal network dynamics are modulated by postnatal stimuli

Neurons in the cerebral cortex and hippocampus discharge synchronously in a brain state-dependent manner to transfer information. Published studies have highlighted the temporal coordination of neuronal activities between the hippocampus and a cortical area, however, how the spatial extent of cortex activity relates to hippocampal activity remains largely unknown. We imaged macroscopic cortical activity while recording hippocampal local field potentials in unanesthetized GCaMP-expressing transgenic mice. We found that cortical activity elevates before and after hippocampal sharp wave ripples (SWR). SWR-associated cortical activities occurred predominantly in vision-related regions including visual, retrosplenial and prefrontal cortex. While pre-SWR cortical activities were frequently observed in awake and sleep states, post-SWR cortical activity decreased significantly in sleep. During hippocampal theta oscillation states, phase-locked oscillations of calcium activity was observed throughout the entire cortex state. Environmental effects on cortico-hippocampal dynamics were also assessed by comparing mice reared in an enriched environment (ENR) or under isolated conditions (ISO). In both SWR and theta oscillations, mice reared in an isolated condition exhibited clearer brain state-dependent dynamics than those reared in an enriched environment. Our data demonstrate that the cortex and hippocampus exhibit heterogeneous activity patterns that characterize brain states, and postnatal experience plays a significant role in modulating these patterns. Significant StatementThe hippocampus is a center for memory formation. However, the memory formed in the hippocampus is not stored forever, but gradually transferred into the cerebral cortex. As an underlying mechanism, phase-locked synchronized activities between the cortex and hippocampus has been hypothesized. However, spatio-temporal dynamics between hippocampus and whole cortical areas remained mostly unknown. We measured cortical calcium activities with hippocampal electroencephalogram (EEG) simultaneously, and found that the activities of widespread cortical areas are temporally associated with hippocampal EEG. The cortico-hippocampal dynamics is primarily regulated by animal awake/sleep state. Even if similar EEG patters were observed, temporal dynamics between the cortex and hippocampus exhibit distinct patterns between awake and sleep period. In addition, animals postnatal experience modulates the dynamics.

neuroscience↗