Early life stress (ELS) yields cognitive impairments of unknown molecular and physiological origin. We found that fragmented maternal care of mice during a neonatal critical period from postnatal days P2–9 elevated dopamine receptor D2R and suppressed D4R expression, specifically within the anterior cingulate cortex (ACC) in only the male offspring. This was associated with poor performance on a two-choice visual attention task, which was acutely rescued in adulthood by local or systemic pharmacological rebalancing of D2R/D4R activity. Furthermore, ELS male mice demonstrated heightened hypothalamic orexin and persistently disrupted sleep. Given that acute sleep deprivation in normally reared male mice mimicked the ACC dopamine receptor subtype modulation and disrupted attention of ELS mice, sleep loss likely underlies cognitive deficits in ELS mice. Likewise, sleep impairment mediated the attention deficits associated with early adversity in human children, as demonstrated by path analysis on data collected with multiple questionnaires for a large child cohort. A deeper understanding of the sex-specific cognitive consequences of ELS thus has the potential to reveal therapeutic strategies for overcoming them.

The basolateral amygdala (BLA) is crucial for the encoding and expression of fear memory, yet it remains unexplored how neural activity in this region is dynamically influenced by distributed circuits across the brain to facilitate expression of fear memory of different ages. Using longitudinal multisite electrophysiological recordings in male mice, we find that the recall of older contextual fear memory is accompanied by weaker, yet more rhythmic, BLA gamma activity which is distally entrained by theta oscillations in both the hippocampal CA1 and the anterior cingulate cortex. Computational modeling with Light Gradient Boosting Machine using extracted oscillatory features from these three regions, as well as with Transformer using raw local field potentials, accurately classified remote from recent memory recall primarily based on BLA gamma and CA1 theta. These results demonstrate in a non-biased manner that multi-regional control of BLA activity serves as reliable neural signatures for memory age-dependent recall mechanisms.

近年，長鎖の機能性RNAであるlong non-coding RNA（lncRNA）が，癌を含めた疾患の病態成立に寄与する事が明らかとなっている．また，lncRNAの中には細胞外小胞（extracellular vesicle；EV）によって細胞間輸送されるものがあり，伝達先の細胞においてシグナルや機能に影響を与える事が分かっている．これらlncRNAとEVの膵発癌，進展における機能解析はほとんどなされていないのが現状であるが，いくつかのlncRNAが膵癌浸潤，転移に重要なプロセスであるepithelial-mesenchymal transition（EMT）を制御する事が示唆されている．膵癌におけるlncRNAの核酸本体としてのエピジェネティックな制御機構及び，EVを介した情報伝達機構を解明する事が，新たな膵癌診断，治療法の開発につながる可能性がある．

Despite the importance of sleep to the cerebral cortex, how much sleep changes cortical neuronal firing remains unclear due to complicated firing behaviors. Here we quantified firing of cortical neurons using Hawkes process modeling that can model sequential random events exhibiting temporal clusters. “Intensity” is a parameter of Hawkes process that defines the probability of an event occurring. We defined the appearance of repetitive firing as the firing intensity corresponding to “intensity” in Hawkes process. Firing patterns were quantified by the magnitude of firing intensity, the time constant of firing intensity, and the background firing intensity. The higher the magnitude of firing intensity, the higher the likelihood that the spike will continue. The larger the time constant of firing intensity, the longer the repetitive firing lasts. The higher the background firing intensity, the more likely neurons fire randomly. The magnitude of firing intensity was inversely proportional to the time constant of firing intensity, and non-REM sleep increased the magnitude of firing intensity and decreased the time constant of firing intensity. The background firing intensity was not affected by the sleep/wake state. Our findings suggest that the cortex is organized such that neurons with a higher probability of repetitive firing have shorter repetitive firing periods. In addition, our results suggest that repetitive firing is ordered to become high frequency and short term during non-REM sleep, while unregulated components of firing are independent of the sleep/wake state in the cortex. Hawkes process modeling of firing will reveal novel properties of the brain.