Research

Our work starts from one view of nature: the rhythm of sleep chooses the fate of memory and emotion. That rhythm takes a different form at each timescale. Within a single theta cycle, it is which few neurons fire at which moment. Across a night, it is how one sleep stage hands over to the next. Over weeks, it is when newly added neurons are welcomed into existing circuits. Our three pillars pursue this one view at these three timescales, with equal weight.

We work with the National Center of Neurology and Psychiatry (NCNP), the International Institute for Integrative Sleep Medicine (IIIS) at the University of Tsukuba, the RIKEN Center for Brain Science (CBS), and researchers in Japan and abroad.

Pillar 1 · Sleep-driven dynamics of memory

睡眠による記憶ダイナミクスの基礎機序

At which moment of sleep’s rhythm must which few neurons fire for a memory to stay?

Basic mechanisms of how sleep — particularly REM sleep — supports memory consolidation and circuit-level integration of newly generated neurons.

Pillar 1 · 1a

Adult-born neurons × REM sleep

Question: How do new neurons born in the adult hippocampus integrate into existing memory circuits during sleep?

The dentate gyrus generates new neurons throughout life. We first showed that ablation of adult-generated neurons degrades previously acquired memories (Arruda-Carvalho & Sakaguchi et al., J Neurosci 2011), and that sparse activity of adult-born neurons during REM sleep is necessary for memory consolidation (Kumar et al., Neuron 2020). Most recently, using activity-dependent tagging and optogenetic manipulation, we provided causal evidence that, during REM sleep, (i) reactivation of a memory ensemble of as few as ~3 adult-born neurons is necessary for fear-memory consolidation, and (ii) synchronization of adult-born-neuron activity to a specific theta phase is essential for fear-memory consolidation (Srinivasan et al., Nature Communications 2025).

Pillar 1 · 1b

Memory remapping, metabolism, and circuit dynamics during sleep

We have mapped how adult-born neuron activity is remapped during fear memory consolidation (Vergara et al., IJMS 2021), identified metabolic fingerprints of fear memory consolidation in the dentate gyrus (Koyanagi et al., Molecular Brain 2021), and developed analysis tools to track the same neurons across 100+ days (Vergara et al., Nature Communications 2025; Chavan et al., Neurobiol Learn Mem 2025).

Key publications: see Publications →

Pillar 2 · Sleep and PTSD

睡眠とPTSD — 病態メカニズムと治療技術開発

Does a disrupted sleep cycle keep trauma memories from fading? We carry the answer into SES, an investigational platform.

We pair animal studies of trauma-related fear memory with clinical studies in patients with PTSD, and translate the findings into a sleep-based therapeutic technology — Sound Exposure during Sleep (SES).

Pursuing PTSD research at Kobe University carries a particular sense of mission. In 1995 this city was struck by the Great Hanshin–Awaji Earthquake, and many in this region have lived with its lasting psychological aftermath. As a laboratory rooted in this place, we take seriously the responsibility of understanding trauma-related conditions and developing therapeutic technologies. This page provides scientific context only — it is not a channel for medical advice, and it is not a recruitment channel for any clinical study.

Pillar 2 · 2a

Animal: pathophysiology of trauma-related fear memory

Using rodent models we have studied the formation and contextualization of fear memory (Fujinaka et al., Molecular Brain 2016), the time course over which fear generalizes after conditioning (Yu et al., BBRC 2021), and the conditions under which extinction can be facilitated and the underlying fear memory itself reshaped in PTSD-like models (Kawakami et al., BBRC 2024). Auditory cues delivered during NREM sleep can modulate fear memory (Purple et al., Scientific Reports 2017), establishing the mechanistic substrate for the clinical SES program.

Pillar 2 · 2b

Clinical: sleep-rhythm signatures of PTSD

In a recent preprint we report what we believe to be the first description of altered NREM–REM cycle transitions in people with PTSD (Sekiba et al., medRxiv 2025; preprint, peer review pending). This signature provides both a candidate biomarker and a hypothesis for how disturbed sleep cycles may underlie persistent fear memory in PTSD.

Pillar 2 · 2c

Clinical: Sound Exposure during Sleep (SES) — therapeutic technology development

Sound Exposure during Sleep (SES) is our laboratory's investigational platform. It delivers individualized auditory cues during specific sleep stages, leveraging endogenous sleep-dependent memory processing to help modulate trauma-related memory processing.

We have successfully completed a medical-institution-led, First-in-Human feasibility study of SES (registered as jRCT1030230706). 13 patients provided informed consent and 6 completed overnight SES. The intervention proved well tolerated: slow-wave sleep was preserved and no adverse events were attributed to the auditory cues, supporting feasibility and safety. Exploratory analyses are described in the preprint (Ino et al., medRxiv 2026).

SES remains an investigational platform; this site provides no medical advice, and the registered study has concluded.

Key publications: see Publications →

Pillar 3 · Sleep-Enabled Neural Regenerative Medicine

睡眠を利用した神経再生医療

Can the rhythm of sleep become the time when newly added neurons join existing circuits?

Across a continuous twenty-year lineage — from the discovery of Galectin-1 as a driver of adult neurogenesis to the integration of grafted cells under theta-band sleep oscillations — we are building toward a regenerative-medicine platform in which sleep itself is the environment that helps newly added neurons join host circuits.

Pillar 3 · 3a

Molecular foundations: drivers of adult neurogenesis

During his time in the Okano laboratory at Keio University, the PI led the discovery that the carbohydrate-binding protein Galectin-1 promotes proliferation of adult neural stem cells (Sakaguchi et al., PNAS 2006), with related US patents (US 7,785,596 and US 7,662,385) co-invented in the same period. This molecular foundation defined the laboratory's long-standing interest in adult-born neurons as a substrate for regenerative repair.

Pillar 3 · 3b

Sleep and adult-born neurons: establishing causality

We established that newly born neurons make a causal contribution to memory (Arruda-Carvalho & Sakaguchi et al., J Neurosci 2011), that their sparse activity during REM sleep is necessary for memory consolidation (Kumar et al., Neuron 2020), and and that, during REM sleep, the reactivation of a minimal ensemble (as few as ~3 such neurons) and the synchronization of adult-born-neuron activity to a specific theta phase are each required for memory consolidation (Srinivasan et al., Nature Communications 2025). Reviews positioning these findings as a bridge from basic neurogenesis to regenerative neuroscience: Akers et al., Stem Cells 2018; Koyanagi & Sakaguchi, Neural Regen Res 2019.

Pillar 3 · 3c

Sleep-coupled circuit integration: the core regenerative technology

Technological underpinnings include the registered patent for our miniature fluorescence microscope (T-Scope, Japanese patent 7299610), the registered patent for the real-time AI sleep-staging device (Japanese patent 7321511), and the closed-loop opto/imaging stack.

Methods we develop & deploy

In vivo

Miniaturized fluorescence microscope

Custom miniscope optimized for freely-moving recording in chronic sleep contexts.

Computation

Real-time sleep AI

Edge-deployable model for closed-loop, stage-specific intervention during sleep.

Genetic tools

Cell-type-specific opto / chemo

Transgenic mouse lines targeting adult-born neurons across the lifespan.