Enhancement of spatial learning by 40 Hz visual stimulation requires parvalbumin interneuron-dependent hippocampal neurogenesis

Yan, H.; Deng, X.; Wang, Y.; Wu, S.; Jun, D.; Yu, M.; Liu, B.; Wang, H.; Pan, Y.; Zhang, Z.; Chen, J.; Walker, T.; Bartlett, P.; Ju, J.; Hou, S.-T.

doi:10.1101/2024.04.28.591481

bioRxiv · 10.1101/2024.04.28.591481

Enhancement of spatial learning by 40 Hz visual stimulation requires parvalbumin interneuron-dependent hippocampal neurogenesis

Yan, H.·Deng, X.·Wang, Y.·Wu, S.·Jun, D.·Yu, M.·Liu, B.·Wang, H.·Pan, Y.·Zhang, Z.·Chen, J.·Walker, T.·Bartlett, P.·Ju, J.·Hou, S.-T.

View original source ↗Export metadata ↓

Abstract

Acute and short-term rhythmic 40 Hz light flicker stimulation has shown promising results in alleviating cognitive impairments in mouse models of Alzheimers disease (AD), stroke, and autism spectrum disorders (ASD). Understanding the long-term impacts and underlying mechanisms is crucial to progress this approach for potential human therapeutic applications. Here, we show that prolonged exposure to 40 Hz light flicker (1 hour per day for 30 days) significantly improved spatial learning and neurogenesis in the dentate gyrus (DG) without harmful behavioral side effects. Mice with transgenic deletion of doublecortin-positive cells (DCXDTR) in the adult hippocampus failed to exhibit enhanced neurogenesis and spatial learning with 40 Hz stimulation. Inactivation or knockout of GABAergic parvalbumin (PV) interneurons reduced the effects of 40 Hz entrainment and neurogenesis enhancement. Mechanistically, the stimulation did not alter the regional microvessel blood flow but significantly raised PV excitability and GABA levels and enhanced inhibitory transmission in the DG. Blocking GABAA receptors reversed the improvements in spatial learning and neurogenesis. These data showed that long-term exposure to 40 Hz light flicker enhances spatial learning through PV-dependent adult neurogenesis, which requires elevated GABA as a critical neurochemical mechanism for sustaining adult neurogenesis. In briefRhythmic 40 Hz light flicker alleviates cognitive impairments in diverse animal models of neurological diseases. Understanding its long-term effects and mechanisms is vital for advancing its therapeutic potential for humans. Here, we show that prolonged exposure to this flicker improves spatial learning and boosts adult neurogenesis in the dentate gyrus. Activation of PV interneurons and GABAergic support for the newborn immature neurons underlie this effect, demonstrating lasting benefits for the treatment of neurological diseases. HighlightsO_LILong-term exposure to 40 Hz light flicker significantly improved spatial learning and neurogenesis in the hippocampus, devoid of adverse effects. C_LIO_LIThe 40 Hz light flicker evoked adult neurogenesis requires the activity of GABAergic inhibitory PV interneurons. C_LIO_LIThe 40 Hz light flicker raised GABA levels and enhanced inhibitory transmission in the DG. C_LIO_LIIncreased GABA serves as a vital neurochemical mechanism to support adult neurogenesis. C_LI

Explore related subjects

neuroscience Preprint

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

Yan, H., Deng, X., Wang, Y., Wu, S., Jun, D., Yu, M., Liu, B., Wang, H., Pan, Y., Zhang, Z., Chen, J., Walker, T., Bartlett, P., Ju, J., Hou, S.-T.. 2024-04-29. Enhancement of spatial learning by 40 Hz visual stimulation requires parvalbumin interneuron-dependent hippocampal neurogenesis. https://doi.org/10.1101/2024.04.28.591481

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Same Movements, Different Skills: How Context Shapes Learning in Humans and Neural Networks

What determines whether experiences are integrated into shared representations or split? Motor skill learning offers a revealing test: when two tasks require an identical sequence of movements, both intuition and theory suggest that practice in one should generalize to the other. Yet we find that changing context can make identical movements different skills. In simple recurrent networks trained on the same sequence across contexts, splitting was greatest when strong contextual inputs coincided with a high initial weight scale; neither alone sufficed. Greater representational separation coincided with separate context-specific learning curves. Humans practicing the same finger sequence while alternating between two performance-irrelevant contexts likewise exhibited context-specific curves, rather than the single continuous trajectory observed when practicing in a single context. State-space modeling favored split learning states in humans and very weakly coupled states in the most context-dependent networks. These findings have broader implications for understanding how learning generalizes across contexts.

neuroscience↗

bioRxiv2026

Postpartum resource scarcity reshapes maternal care, offspring prioritization, and the steroid-sensitive medial preoptic area

Parental care requires balancing offspring needs with environmental constraints, yet how resource scarcity alters the organization of maternal responses remains poorly understood. Here, we examined maternal behavior, offspring prioritization, and steroid receptor-associated extracellular matrix organization in postpartum rats exposed to limited bedding and nesting (LBN) or control conditions with ample nesting materials. LBN increased pup-directed and reduced self-directed behaviors but also increased behavioral entropy, a measure of behavioral fragmentation, indicating less predictable caregiving sequences. LBN dams preferentially retrieved male pups first, whereas control dams preferentially retrieved females first. LBN also increased the proportion of pup-investigation time directed toward males compared with controls. In offspring on postnatal day 10, corticosterone was elevated in female but not male LBN pups, a pattern that paralleled the maternal male bias. To identify associated neurobiological changes, we assessed steroid receptors and extracellular matrix organization in the medial preoptic area (mPOA), a key region for maternal behavior. LBN increased numbers of estrogen receptor (ER)- and androgen receptor (AR)-immunoreactive cells, reduced perineuronal net (PNN) abundance, and decreased receptor-positive cell enwrapment. Because PNNs constrain structural plasticity, these findings suggest that the postpartum environment alters the organization of steroid receptor-associated extracellular matrix, potentially modulating experience-dependent plasticity in neurosteroid-sensitive circuits. In sum, LBN increases the levels of maternal engagement while reshaping its temporal organization and allocation, accompanied by selective remodeling of steroid-sensitive preoptic architecture. Therefore, maternal adaptation to adversity may be better understood as changes in caregiving allocation strategies rather than a simple gain or loss of maternal care.

neuroscience↗

bioRxiv2026

The Computational Grammar of Human Behaviour in a Biological Environment

Human behaviour unfolds as an extended stream of spontaneous actions shaped by environmental demands and the agent's goals. The organisation of these actions, situated between setting abstract goals and concrete movement execution, remains poorly characterised. Here, we introduce DynaClade, an unsupervised temporal action segmentation algorithm for human full-body motion capture data, and apply it to freely moving participants navigating ecologically realistic risky foraging environments in virtual reality. DynaClade identifies discrete actions whose kinematic characteristics and spatial distributions correspond to environmental affordances, supporting the validity of the approach. Among these actions, we discovered a hitherto undescribed movement pattern defined by increased body sway without locomotion. Action sequences were highly non-random and showed clear history dependence beyond first-order Markov structure, most of which was explained by a second-order prediction. This higher-order structure was well captured in a hidden Markov model, in which some of the observed actions were associated with more than one latent state. Each of these latent states corresponded to the same action in a distinct action context. These findings suggest that spontaneous human actions are predominantly selected based on the current action and context, rather than following pre-planned or habitually assembled sequences.

neuroscience↗