Biology subjects

Merkler, M.

Publications and source records attributed to Merkler, M..

3 recordsLinked to original sources

bioRxiv2026

Distributed state-dependent neural ensembles across sleep stages

Sleep architecture is organized by neural ensembles operating across multiple timescales, yet the organizing principles remain unclear. By monitoring neural populations across >40 brain regions in mice, we reveal a distributed sleep code spanning multiple temporal scales. On a slow (minutes-to-seconds) timescale, vigilance state reorganized brain-wide firing and was decodable from every region, with REM sleep emerging as a globally activated state. State transitions followed low-dimensional trajectories, with cortical and subcortical ensembles evolving in antiphase at wake-NREM boundaries but in register during transitions into REM sleep. On a fast (seconds-to-milliseconds) timescale, NREM slow/delta oscillations served as a global rhythm while hierarchically nesting spindles, sharp-wave ripples, and pontine (P) waves, whereas REM theta-P-wave coupling coordinated firing across regions. Regional sleep-related activities covaried with neuromodulatory innervation, while infraslow, history-dependent firing dynamics tracked NREM-REM cycles. Together, these findings provide a cell-resolved atlas of distributed neural population dynamics across sleep stages.

neuroscience↗

bioRxiv2025

Multi-fiber array-based photometry system for multi-regional functional mapping in the mouse brain

Mesoscopic functional brain mapping is essential to better understanding of various brain functions and dysfunctions. However, accessing distributed neural circuits in mammalian brain regions remains a significant challenge. While fiber photometry is a versatile optical approach, existing methods often suffer from invasiveness and scalability. Here we present an affordable multi-fiber array (MFA)-based photometry system to monitor neural signals across multiple regions. Our system comprises a custom-designed MFA utilizing 50-{micro}m diameter optical fibers and off-the-shelf optical components. To demonstrate the systems versatility, we monitored GABAergic population activity using jGCaMP8s across multiple brain regions in head-fixed, awake mice. By combining with pupillometry, we identified state-dependent, region-specific GABAergic dynamics. Our MFA-based photometry system opens new avenues for investigating state-dependent neural dynamics at the mesoscopic level. To facilitate wider adoption, all codes and resources are publicly available on GitHub (https://github.com/Sakata-Lab/MFA).

neuroscience↗

bioRxiv2022

Developmental overproduction of cortical superficial neurons impairs adult auditory cortical processing

While evolutionary cortical expansion is thought to underlie the evolution of human cognitive capabilities, excessive developmental expansion can lead to megalencephaly, often found in neurodevelopmental disorders such as autism spectrum disorder. Still, little is known about how the overproduction of cortical neurons during development affects cortical processing and behavior in later life. Here we show that the developmental overproduction of cortical superficial neurons impairs auditory processing in mice. We took advantage of a WNT/{beta}- catenin signaling inhibitor, XAV939, to overproduce cortical superficial excitatory neurons during development. XAV939-treated adult mice exhibited a longer reaction time and a higher threshold to detect acoustic stimuli behaviorally. This mouse model also demonstrated abnormal auditory cortical processing depending on experimental conditions: in a passive listening condition, we observed lower beta power and lower spontaneous and auditory-evoked activity in putative excitatory cells whereas higher pre-stimulus spontaneous activity in excitatory cells is associated with failing to detect auditory stimuli behaviorally. On the other hand, the auditory thalamus did not show any significant difference in neural firing between XAV939-treated and control groups. Furthermore, functional monosynaptic connections were significantly reduced between cortical putative excitatory cells. Altogether, our results suggest that the atypical auditory detectability of XAV939-treated animals can be explained by abnormal auditory cortical processing. Although the expansion of cortical size is evolutionarily advantageous, an abnormal expansion during development can result in detrimental effects on cortical processing and perceptual behavior in adulthood.

neuroscience↗