Altered expression of peripheral myelin protein 22 (PMP22) results in demyelinating peripheral neuropathy. PMP22 exhibits a highly restricted tissue distribution with marked expression in the myelinating Schwann cells of peripheral nerves. Auditory and vestibular Schwann cells and the afferent neurons also express PMP22, suggesting a unique role in hearing and balancing. Indeed, neuropathic patients diagnosed with PMP22-linked hereditary neuropathies often present with auditory and balance deficits, an understudied clinical complication. To investigate the mechanism by which abnormal expression of PMP22 may cause auditory and vestibular deficits, we studied gene-targeted PMP22 -null mice. PMP22 -null mice exhibit an unsteady gait, have difficulty maintaining balance, and live for only ∼3–5 weeks relative to unaffected littermates. Histological analysis of the inner ear revealed reduced auditory and vestibular afferent nerve myelination and profound Na+ channel redistribution without PMP22. Yet, Na+ current...

Automated behavior quantification in socially interacting animals requires accurate tracking. While many methods have been very successful and highly generalizable to different settings, issues of mistaken identities and lost information on key anatomical features are common, although they can be alleviated by increased human effort in training or post-processing. We propose a markerless video-based tool to simultaneously track two interacting mice of the same appearance in controlled settings for quantifying behaviors such as different types of sniffing, touching, and locomotion to improve tracking accuracy under these settings without increased human effort. It incorporates conventional handcrafted tracking and deep-learning-based techniques. The tool is trained on a small number of manually annotated images from a basic experimental setup and outputs body masks and coordinates of the snout and tail-base for each mouse. The method was tested on several commonly used experimental conditions including bedd...

The medial habenula (MHb) has been identified as the limiting factor for nicotine intake and facilitating nicotine withdrawal. However, few studies have assessed MHb neuronal excitability in response to nicotine, and, currently, a gap in knowledge is present for finding behavioral correlates to neuronal excitability in the region. Moreover, no study to date has evaluated sex or nicotine dosage as factors of excitability in the MHb. Here, we utilized an e-vape self-administration (EVSA) model to determine differences between sexes with different nicotine dosages ± menthol. Following this paradigm, we employed patch-clamp electrophysiology to assess key metrics of MHb neuronal excitability in relation to behavioral endpoints. We observed female mice self-administered significantly more than males, regardless of dosage. We also observed a direct correlation between self-administration behavior and MHb excitability with low-dose nicotine + menthol in males. Conversely, a high dose of nicotine ± menthol yields ...

Content-to-context binding is crucial for working memory performance. Using a dual-serial retrocueing (DSR) task on oriented gratings, [Yu et al. (2020)][1] found that content (orientation) of both prioritized and unprioritized memory items (PMI; UMI) was represented simultaneously in visual cortex, while their context (location) was represented in intraparietal sulcus (IPS), with a priority-based remapping of the representation of content and context of the UMI in each region, respectively. This registered report acquired fMRI of 24 healthy adults while they performed a DSR task with location as the to-be-reported content and orientation as the task-relevant context. We contrasted three accounts: domain-dependent, the engagement of visual and parietal regions depends on the feature domain (orientation vs location); functional, the engagement of these regions depends on their function (content vs context); and hybrid—a combination of the domain-dependent account and the additional stipulation that IPS enco...

Learning and adaptation during sources of threat and safety are critical mechanisms for survival. The prelimbic (PL) and infralimbic (IL) subregions of the medial prefrontal cortex (mPFC) have been broadly implicated in the processing of threat and safety. However, how these regions regulate threat and safety during naturalistic conditions involving thermal challenge still remains elusive. To examine this issue, we developed a novel paradigm in which adult mice learned that a particular zone that was identified with visuospatial cues was associated with either a noxious cold temperature (“threat zone”) or a pleasant warm temperature (“safety zone”). This led to the rapid development of avoidance behavior when the zone was paired with cold threat or approach behavior when the zone was paired with warm safety. During a long-term test without further thermal reinforcement, mice continued to exhibit robust avoidance or approach to the zone of interest, indicating that enduring spatial-based memories were forme...

Lumbar erector spinae (LES) contribute to spine postural and voluntary control. Transcranial magnetic stimulation (TMS) preferentially depolarizes different neural circuits depending on the direction of electrical currents evoked in the brain. Posteroanterior current (PA-TMS) and anteroposterior (AP-TMS) current would, respectively, depolarize neurons in the primary motor cortex (M1) and the premotor cortex. These regions may contribute differently to LES control. This study examined whether responses evoked by PA- and AP-TMS are different during the preparation and execution of LES voluntary and postural tasks. Participants performed a reaction time task. A Warning signal indicated to prepare to flex shoulders (postural; n  = 15) or to tilt the pelvis (voluntary; n  = 13) at the Go signal. Single- and paired-pulse TMS (short-interval intracortical inhibition—SICI) were applied using PA- and AP-TMS before the Warning signal (baseline), between the Warning and Go signals (preparation), or 30 ms before the L...

Activity-dependent neuronal plasticity is crucial for animals to adapt to dynamic sensory environments. Traditionally, it has been investigated using deprivation approaches in animal models primarily in sensory cortices. Nevertheless, emerging evidence emphasizes its significance in sensory organs and in subcortical regions where cranial nerves relay information to the brain. Additionally, critical questions started to arise. Do different sensory modalities share common cellular mechanisms for deprivation-induced plasticity at these central entry points? Does the deprivation duration correlate with specific plasticity mechanisms? This study systematically reviews and meta-analyzes research papers that investigated visual, auditory, or olfactory deprivation in rodents of both sexes. It examines the consequences of sensory deprivation in homologous regions at the first central synapse following cranial nerve transmission (vision - lateral geniculate nucleus and superior colliculus; audition - ventral and dor...

A current hypothesis to explain the limited recovery following brain and spinal cord trauma stems from the dogma that neurons in the mammalian central nervous system lack the ability to regenerate their axons after injury. Serotonin (5-HT) neurons in the adult brain are a notable exception in that they can slowly regrow their axons following chemical or mechanical lesions. This process of regrowth occurs without intervention over several months and results in anatomical recovery that approximates the preinjured state. During development, serotonin is a trophic factor, playing a role in both cell survival and axon growth. Additionally, some studies have shown that stroke patients treated after injury with serotonin selective reuptake inhibitors (SSRIs) appeared to have improved recovery. To test the hypothesis that serotonin can influence the regrowth of 5-HT axons, mice received a high dose of para -chloroamphetamine (PCA) to induce widespread retrograde degeneration of 5-HT axons. Then, after a short rest...

Electroencephalography (EEG) is an indispensable tool in epilepsy, sleep, and behavioral research. In rodents, EEG recordings are typically performed with metal electrodes that traverse the skull into the epidural space. In addition to requiring major surgery, intracranial EEG is difficult to perform for more than a few electrodes, is time-intensive, and confounds experiments studying traumatic brain injury. Here, we describe an open-source cost-effective refinement of this technique for chronic mouse EEG recording. Our alternative two-channel (EEG2) and sixteen-channel high-density EEG (HdEEG) arrays use electrodes made of the novel, flexible 2D nanomaterial titanium carbide (Ti3C2T x ) MXene. The MXene electrodes are placed on the surface of the intact skull and establish an electrical connection without conductive gel or paste. Fabrication and implantation times of MXene EEG electrodes are significantly shorter than the standard approach, and recorded resting baseline and epileptiform EEG waveforms are ...

Spinal cord injury (SCI) has become one of the common and serious diseases affecting patients’ motor functions. The small extracellular vesicles secreted by bone marrow mesenchymal stem cells (BMSCs) have shown a promising prospect for the treatment of neurological diseases. BMSCs were collected from rat bones. Osteogenic and adipogenic differentiation of BMSCs was further determined. Small extracellular vesicles were obtained by high-speed centrifugation. Dual-luciferase reporter assay was performed to demonstrate the targeting of miR-211-5p to the cyclooxygenase 2 (COX2) mRNA. qRT-PCR and Western blot assay were used for the detection of the mRNA and protein expression. ELISA was performed to estimate the levels of proinflammatory factors in spinal cord tissues. Our results showed that miR-211-5p targeted COX2 mRNA and regulated the protein expression of COX2 in BMSCs. Extracellular vesicles released from miR-211-5p-overexpressed BMSCs ameliorated SCI-induced motor dysfunction and motor evoked potential ...