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...

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...

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...

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 (...

We often need to decide whether the object we look at is also the object we look for. When we look for one specific object, this process can be facilitated by feature-based attention. However, when we look for many objects at the same time (e.g., the products on our shopping list), such a strategy may no longer be possible, as research has shown that we can actively prepare to detect only one or two objects at a time. Therefore, looking for multiple objects additionally requires long-term memory search, slowing down decision-making. Interestingly, however, previous research has shown that distractor objects can be efficiently rejected during memory search when they are from a different category than the items in the memory set. Here, using EEG, we show that this efficiency is supported by top-down attention at the category level. In Experiment 1, human participants (both sexes) performed a memory search task on individually presented objects from different categories, most of which were distractors. We obs...

In the article “Asymmetric Voltage Attenuation in Dendrites Can Enable Hierarchical Heterosynaptic Plasticity,” by Toviah Moldwin, Menachem Kalmenson, and Idan Segev, which was published online on …

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 ...

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...