We explore the world by constantly shifting our focus of attention toward salient stimuli and then disengaging from them in search of new ones. The alpha rhythm (8–13 Hz) has been suggested as a pivotal neural substrate of these attentional shifts, due to its local synchronization and desynchronization that suppress irrelevant cortical areas and facilitate relevant areas, a phenomenon called alpha lateralization. Whether alpha lateralization tracks the focus of attention from orienting toward a salient stimulus to disengaging from it is still an open question. We addressed it by leveraging the phenomenon of inhibition of return (IOR), consisting of an initial facilitation in response times (RTs) for stimuli appearing at an exogenously cued location, followed by a suppression of that location. Our behavioral data from human participants showed a typical IOR effect with both early facilitation and subsequent inhibition. In contrast, alpha lateralized in the cued direction after the behavioral facilitation ef...

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 ...

The paraventricular thalamic nucleus (PVT) is a brain region that mediates aversive and reward-related behaviors as shown in animals exposed to fear conditioning, natural rewards, or drugs of abuse. However, it is unknown whether manipulations of the PVT, in the absence of external factors or stimuli (e.g., fear, natural rewards, or drugs of abuse), are sufficient to drive reward-related behaviors. Additionally, it is unknown whether drugs of abuse administered directly into the PVT are sufficient to drive reward-related behaviors. Here, using behavioral as well as pathway and cell-type specific approaches, we manipulate PVT activity as well as the PVT-to-nucleus accumbens shell (NAcSh) neurocircuit to explore reward phenotypes. First, we show that bath perfusion of morphine (10 µm) caused hyperpolarization of the resting membrane potential, increased rheobase, and decreased intrinsic membrane excitability in PVT neurons that project to the NAcSh. Additionally, we found that direct injections of morphine (...

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...

Spinal cord injury (SCI) often results in various long-term sequelae, and chronically injured spinal cords exhibit a refractory feature, showing a limited response to cell transplantation therapies. To our knowledge, no preclinical studies have reported a treatment approach with results surpassing those of treatment comprising rehabilitation alone. In this study of rats with SCI, we propose a novel combined therapy involving a semaphorin 3A inhibitor (Sema3Ai), which enhances axonal regeneration, as the third treatment element in combination with neural stem/progenitor cell transplantation and rehabilitation. This comprehensive therapeutic strategy achieved significant improvements in host-derived neuronal and oligodendrocyte differentiation at the SCI epicenter and promoted axonal regeneration even in the chronically injured spinal cord. The elongated axons established functional electrical connections, contributing to significant enhancements in locomotor mobility when compared with animals treated with ...

Estimating durations between hundreds of milliseconds and seconds is essential for several daily tasks. Explicit timing tasks, which require participants to estimate durations to make a comparison (time for perception) or to reproduce them (time for action), are often used to investigate psychological and neural timing mechanisms. Recent studies have proposed that mechanisms may depend on specific task requirements. In this study, we conducted electroencephalogram (EEG) recordings on human participants as they estimated intervals in different task contexts to investigate the extent to which timing mechanisms depend on the nature of the task. We compared the neural processing of identical visual reference stimuli in two different tasks, in which stimulus durations were either perceptually compared or motorically reproduced in separate experimental blocks. Using multivariate pattern analyses, we could successfully decode the duration and the task of reference stimuli. We found evidence for both overlapping t...

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...

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...