Hearing impairment (HI) disrupts social interaction by hindering the ability to follow conversations in noisy environments. While hearing aids (HAs) with noise reduction (NR) partially address this, the “cocktail-party problem” persists, where individuals struggle to attend to specific voices amidst background noise. This study investigated how NR and an advanced signal processing method for compensating for nonlinearities in Electroencephalography (EEG) signals can improve neural speech processing in HI listeners. Participants wore HAs with NR, either activated or deactivated, while focusing on target speech amidst competing masker speech and background noise. Analysis focused on temporal response functions to assess neural tracking of relevant target and masker speech. Results revealed enhanced neural responses (N1 and P2) to target speech, particularly in frontal and central scalp regions, when NR was activated. Additionally, a novel method compensated for nonlinearities in EEG data, leading to improved...

High-frequency stimulation (HFS)-induced long–term potentiation (LTP) is generally regarded as a homosynaptic Hebbian-type LTP, where synaptic changes are thought to occur at the synapses that project from the stimulation site and terminate onto the neurons at the recording site. In this study, we first investigated HFS-induced LTP on urethane-anesthetized rats and found that cortical HFS enhances neural responses at the recording site through the strengthening of local connectivity with nearby neurons at the stimulation site rather than through synaptic strengthening at the recording site. This enhanced local connectivity at the stimulation site leads to increased output propagation, resulting in signal potentiation at the recording site. Additionally, we discovered that HFS can also nonspecifically strengthen distant afferent synapses at the HFS site, thereby expanding its impact beyond local neural connections. This form of plasticity exhibits a neo-Hebbian characteristic as it exclusively manifests in ...

Acute ischemic stroke (AIS) is a severe neurological disease associated with Th17/Treg cell imbalance and dysregulation of the Wnt/β-catenin signaling pathway. This study investigates whether miR-155 inhibition can activate Wnt/β-catenin signaling, improve Th17/Treg balance, and provide neuroprotection against stroke. We conducted a multilevel experimental design, including high-throughput sequencing, bioinformatics analysis, in vivo mouse models, and in vitro cell experiments. High-throughput sequencing revealed significant differential gene expression between the miR-155 antagomir–treated and control groups (BioProject: PRJNA1152758). Bioinformatics analysis identified key genes linked to Wnt/β-catenin signaling and Th17/Treg imbalance. In vitro experiments confirmed that miR-155 inhibition activated Wnt/β-catenin signaling and improved Th17/Treg ratios. In vivo studies demonstrated that miR-155 antagomir treatment provided significant neuroprotection against AIS. These findings suggest that targeting mi...

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 proprietary software. Fu...

A common impairment in aging is age-related hearing loss (presbycusis), which manifests as impaired spectrotemporal processing. Presbycusis can be caused by a dysfunction of the peripheral and central auditory system, and these dysfunctions might differ between the sexes. To date, the circuit mechanisms in the central nervous system responsible for age-related auditory dysfunction remain mostly unknown. In the auditory cortex (ACtx), aging is accompanied by alteration in normal inhibitory (GABA) neurotransmission and changes in excitatory (NMDA and AMPA) synapses, but which circuits are affected has been unclear. Here we investigated how auditory cortical microcircuits change with age and if sex-dependent differences existed. We performed laser-scanning photostimulation (LSPS) combined with whole-cell patch-clamp recordings from layer (L) 2/3 cells in the primary auditory cortex (A1) in young adult (2–3 months) and aged (older than 18 months) male and female CBA/CaJ mice which have normal peripheral hearin...

The perception of scenes is associated with processing in a network of scene-selective regions in the human brain. Prior research has identified a posterior–anterior bias within this network. Posterior scene regions exhibit preferential connectivity with early visual and posterior parietal regions, indicating a role in representing egocentric visual features. In contrast, anterior scene regions demonstrate stronger connectivity with frontoparietal control and default mode networks, suggesting a role in mnemonic processing of locations. Despite these findings, evidence linking connectivity in these regions to cognitive scene processing remains limited. In this preregistered study, we obtained cognitive behavioral measures alongside resting-state fMRI data from a large-scale public dataset to investigate interindividual variation in scene processing abilities relative to the functional connectivity of the scene network. Our results revealed substantial individual differences in scene recognition, spatial mem...

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 considered as a complement...

The behavioral interactions between adults and newborns are decisive for the fitness and the survival of offspring across the animal kingdom. In laboratory mice, while virgin females display caregiving behaviors, virgin males are rather neglectful or aggressive toward pups. Despite the importance of these behavioral variations, the underlying neural mechanisms remain poorly understood. Brain regions encoding these behaviors may exhibit sex-dependent functional differences at the baseline. Additionally, these structures might undergo sex-specific plasticity after adults interact with the offspring. Emerging evidence suggests sex-based differences in input connectivity, genetics, and receptor expression of the epithalamic lateral habenula (LHb). Moreover, LHb neuronal activity is instrumental for adult–newborn interactions. However, whether LHb neuronal function varies between sexes and/or undergoes adaptations following interactions with pups has not been fully investigated. In this study, we used in vivo a...

Breathing is a complex neuromuscular process vital to sustain life. In preclinical animal models, the study of respiratory motor control is primarily accomplished through neurophysiologic recordings and functional measurements of respiratory output. Neurophysiologic recordings that target neural or muscular output via direct nerve recordings or respiratory muscle electromyography (EMG) are commonly collected during anesthetized conditions. While offering tight control of experimental preparations, the use of anesthesia results in respiratory depression, may impact cardiovascular control, eliminates the potential to record volitional nonventilatory behaviors, and can limit translation. Since the diaphragm is a unique muscle which is rhythmically active and difficult to access, placing diaphragm EMGs to collect chronic recordings in awake animals is technically challenging. Here, we describe methods for fabricating and implanting indwelling diaphragm EMG electrodes to enable recordings from awake rodents for...

The adrenal medulla is packed with chromaffin cells, modified postganglionic sympathetic neurons that secrete the catecholamines, epinephrine and norepinephrine, during the fight-or-flight response. Sometimes overlooked is a population of immune cells that also resides within the gland but whose distribution and function are not clear. Here I examine the location of CD45+ hematopoietic cells in the mouse adrenal medulla and show the majority are F4/80+/Lyz2+ macrophages. These cells are present from early postnatal development and widely distributed. Anatomically they are associated with chromaffin cells, found aligned alongside synapsin-IR neuronal varicosities and juxtaposed to CD31-IR blood vessels. Using Lyz2cre-GCaMP6f mice to quantify calcium signaling in macrophages revealed these cells respond directly and indirectly to a wide variety of neuromodulators, including pre- and postganglionic transmitters and systemic hormones. Purinergic agonists, histamine, acetylcholine, and bradykinin rapidly and re...