Motor skill learning enables organisms to interact effectively with their environment, relying on neural mechanisms that integrate sensory feedback with motor output. While sensory feedback, such as auditory cues linked to motor actions, enhances motor performance in humans, its mechanism of action is poorly understood. Developing a reliable animal model of augmented motor skill learning is crucial to begin dissecting the biological systems that underpin this enhancement. We hypothesized that continuous auditory feedback during a motor task would promote complex motor skill acquisition in mice. We developed a closed-loop system using DeepLabCut for real-time markerless tracking of mouse forepaw movements with high processing speed and low latency. By encoding forepaw movements into auditory tones of different frequencies, mice received continuous auditory feedback during a reaching task requiring vertical displacement of the left forepaw to a target. Adult mice were trained over 4 d wi

Transgenic mice provide unprecedented access to manipulate and visualize neural circuits; however, those on a C57BL/6 background develop progressive hearing loss, significantly confounding systems-level and behavioral analysis. While outbreeding can limit hearing loss, it introduces strain variability and complicates the generation of complex genotypes. Here, we propose an approach to preserve hearing by crossing transgenic mice with congenic B6.CAST- Cdh23Ahl + mice, which maintain low-threshold hearing into adulthood. Widefield and two-photon imaging of the auditory cortex revealed that 2.5-month-old C57BL/6 mice exhibit elevated thresholds to high-frequency tones and widespread cortical reorganization, with most neurons responding best to lower frequencies. In contrast, Ahl+ C57BL/6 mice exhibited robust neural responses across tested frequencies and sound levels (4–64 kHz, 30–90 dB SPL) and retained low thresholds into adulthood. Our approach offers a cost-effective solution for ge

Functional ultrasound (fUS) imaging is a well-established neuroimaging technology that offers high spatiotemporal resolution and a large field of view. Typical strategies for analyzing fUS data comprise either region-based averaging, typically based on reference atlases, or correlation with experimental events. Nevertheless, these methodologies possess several inherent limitations, including a restricted utilization of the spatial dimension and a pronounced bias influenced by preconceived notions about the recorded activity. In this study, we put forth single-voxel clustering as a third method to address these issues. A comparison was conducted between the three strategies on a typical dataset comprising visually evoked activity in the superior colliculus in awake mice. The application of single-voxel clustering yielded the generation of detailed activity maps, which revealed a consistent layout of activity and a clear separation between hemodynamic responses. This method is best consi

To develop reparative therapies for neurological disorders like multiple sclerosis (MS), we need to better understand the physiology of loss and replacement of oligodendrocytes, the cells that make myelin and are the target of damage in MS. In vivo two-photon fluorescence microscopy allows direct visualization of oligodendrocytes in the intact brain of transgenic mouse models, promising a deeper understanding of the longitudinal dynamics of replacing oligodendrocytes after damage. However, the task of tracking the fate of individual oligodendrocytes requires extensive effort for manual annotation and is especially challenging in three-dimensional images. While several models exist for annotating cells in two-dimensional images, few models exist to annotate cells in three-dimensional images and even fewer are designed for tracking cells in longitudinal imaging. Notably, existing options often come with a substantial financial investment, being predominantly commercial or confined to pro

Observing lip movements of a speaker facilitates speech understanding, especially in challenging listening situations. Converging evidence from neuroscientific studies shows stronger neural responses to audiovisual stimuli compared with audio-only stimuli. However, the interindividual variability of this contribution of lip movement information and its consequences on behavior are unknown. We analyzed source-localized magnetoencephalographic responses from 29 normal-hearing participants (12 females) listening to audiovisual speech, both with and without the speaker wearing a surgical face mask, and in the presence or absence of a distractor speaker. Using temporal response functions to quantify neural speech tracking, we show that neural responses to lip movements are, in general, enhanced when speech is challenging. After controlling for speech acoustics, we show that lip movements contribute to enhanced neural speech tracking, particularly when a distractor speaker is present. Howeve