eNeuro最新文献

Attachment theory offers an important clinical framework for understanding and treating negative effects of early life adversity. Attachment styles emerge during critical periods of development in response to caregivers' ability to consistently meet their offspring's needs. Attachment styles are classified as secure or insecure (anxious, avoidant, or disorganized), with rates of insecure attachment rising in high-risk populations and correlating with a plethora of negative health outcomes throughout life. Despite its importance, little is known about the neural basis of attachment. Work in rats has demonstrated that limited bedding and nesting (LB) impairs maternal care and produces abnormal maternal attachment linked to increased pup corticosterone. However, the effects of LB on attachment-like behavior have not been investigated in mice where additional genetic and molecular tools are available. Furthermore, no group has utilized home-cage monitoring to link abnormal maternal care with deficits in attachment-like behavior. Using home-cage monitoring, we confirmed a robust increase in maternal fragmentation among LB dams. Abnormal maternal care was correlated with elevated corticosterone levels on postnatal day 7 (P7) and a stunted growth trajectory that persisted later in life. LB did not alter maternal buffering at P8 or maternal preference at P18, indicating that certain attachment-like behaviors remain unaffected despite exposure to high levels of erratic maternal care. However, LB male and female pups vocalized less in response to maternal separation at P8, did not readily approach their dam at P13, and exhibited higher anxiety-like behavior at P18, suggesting that LB induces avoidant-like attachment deficits in mice.

Listening effort reflects the cognitive and motivational resources allocated to speech comprehension, particularly under challenging conditions. Visual cues are known to enhance speech perception, potentially by reducing the cognitive demands of the task. However, the neurophysiological mechanisms underlying this facilitation, especially in terms of effort-related changes, remain unclear. In this study, we combined pupillometry and electroencephalography (EEG) to investigate how visual speech cues modulate cognitive effort during speech recognition. Twenty-two participants (seven females) performed a speech-in-noise task under three modalities: (1) auditory-only, (2) audiovisual, and (3) visual-only. Task difficulty was manipulated via signal-to-noise ratio (SNR) in the first two modalities. Firstly, we found an inverted U-shape relationship between pupil dilation and frontal midline theta with SNR for audiovisual and auditory-only speech, consistent with prior models of effort allocation. Secondly, we observed the SNR at which the neurophysiological measures peaked was at a lower SNR for audiovisual speech. Surprisingly, we found pupil dilation to be larger overall in audiovisual speech, while frontal midline theta did not show differences in either modality. These findings highlight the complexity of interpreting physiological markers of effort and suggest that visual cues may alter the temporal dynamics or resource allocation strategies during speech processing. Our results support the extension of auditory-based models of listening effort to audiovisual contexts and underscore the value of integrating multimodal neurophysiological measures to better understand the cognitive and neural mechanisms of effortful listening.

Identifying neural signatures of slow-wave sleep (SWS) is important for a number of reasons including diagnosing potential sleep disorders and examining its role in memory consolidation ( Diekelmann and Born, 2010; Klinzing et al., 2019; Brodt et al., 2023). Studies of sleep in the common marmoset (Callithrix jacchus) have revealed similarities to humans and other nonhuman primates, including distinct sleep stages ( Crofts et al., 2001) and diurnal sleep patterns ( Hoffmann et al., 2012). Advances in applying wireless technology for recording neural activity during natural, unrestrained behaviors ( Walker et al., 2021) position the marmoset as an excellent model for studying sleep-related neural activity associated with learning. Here, we identify putative SWS epochs based on the spatially correlated activity of local field potentials (LFPs) recorded from a multielectrode planar array implanted in the sensorimotor cortex of two marmosets (one female and one male). The average correlation of the LFP signal measured between electrodes decreased gradually with the distance between pairs. We modeled this spatial structure as an exponential decay function, where the spatial decay constant varied significantly over time, reaching its lowest values during epochs where LFP power dynamics were consistent with SWS. These periods of widespread high correlations across the sensorimotor cortex closely matched SWS identification commonly used in rodent models based on the changes in power in the gamma (30-60 Hz) and delta/slow oscillation (0.1-4 Hz) frequency bands. These findings demonstrate that putative SWS epochs can be reliably identified using spatially correlated LFP activity across the sensorimotor cortex.

Higher education (HE) is undergoing rapid transformation, shaped as a result of the COVID-19 pandemic, the expansion of digital learning, and the increasing presence of artificial intelligence (AI). For educators, these shifts raise important questions about their evolving purpose and responsibilities. In this commentary, we reflect on the role of bioscience educators in the United Kingdom, highlighting the enduring need for human connection, empathy, and belonging in teaching, alongside the integration of digital tools. We discuss changing student motivations, the necessity of flexible and inclusive learning environments, and the balance between traditional practices and innovative pedagogies. Practical training, active learning, and responsible engagement with emerging technologies remain central to equipping students with transferable skills such as adaptability, critical thinking, and resilience. We argue that while digital innovations can enhance accessibility and engagement, they cannot replace the uniquely human dimensions of teaching. Ultimately, bioscience educators must embrace their dual role as facilitators and lifelong learners, modeling curiosity, vulnerability, and inclusivity to empower students to thrive in an increasingly complex world.

Exposure to early life stress (ELS) can exert long-lasting impacts on emotional regulation. The corticolimbic system including the basolateral amygdala (BLA), ventral hippocampus (vHIP), and the medial prefrontal cortex (mPFC) plays a key role in fear learning. Using the limited bedding paradigm (LB), we examined the functional consequences of ELS on excitatory and inhibitory tone in the prelimbic (PL) mPFC after fear conditioning in rats. In adults, LB exposure enhanced in vivo glutamate release in the PL mPFC during fear conditioning in male, but not female offspring. In contrast, the glutamate response to fear conditioning was diminished in LB-exposed pre-adolescent males, but not females. We investigated whether reduced glutamatergic inputs and/or elevated inhibitory tone might contribute to the diminished glutamate response in the mPFC following LB in pre-adolescent male rats. Indeed, we found that LB exposure specifically increased the activation of PV, but not SST interneurons in layer V, but not layer II/III of the PL mPFC in fear-exposed pre-adolescent males. Presynaptic glutamate release probability was reduced by LB exposure in layer V, but increased in layer II/III of the PL mPFC. These functional changes might be related to the LB-induced alterations in the bilaminar distribution of BLA and vHIP projections to the PL mPFC we observed in pre-adolescent males. Overall, our findings suggest that ELS modifies glutamate release and PL mPFC function during fear conditioning in a sex- and age-dependent fashion, likely through layer-specific shifts in excitation/inhibition balance.

Abrupt onsets reflexively shift covert spatial attention. Recent work demonstrated that trial-to-trial information about the probability of a peripheral onset modulated the magnitude of the attentional cueing effect (low probability > high probability). Although onsets were physically identical, pupil responses could have been modulated by information about the probability of the onset's appearance. Specifically, anticipatory constrictions may have preceded high-probability onsets. Here, we tested this hypothesis using centrally presented, luminance-matched onset-probability signals. For half the participants, vertical signaled high probability (0.8) of onset appearance, while horizontal signaled low probability (0.2). Contingencies were reversed for the other half. Participants fixated the onset-probability signal for 2,000 ms before the onset was briefly presented or omitted, in line with the signaled probability. To maintain engagement, participants completed a simple localization task. Preliminary evidence for an anticipatory reduction in the pupil area was obtained in Experiment 1. However, this effect disappeared in Experiment 2 with a larger replication sample. Exploratory analyses uncovered a violation of a fundamental methodological assumption: despite being task-irrelevant and perfectly luminance-matched, vertical onset-probability signals consistently generated smaller pupil areas, relative to horizontal signals in both Experiments 1 and 2. Interestingly, this "orientation effect" was stronger in the second half of the experimental session, and in a third experiment, we significantly reduced its magnitude by changing the locations of the task-relevant stimuli. In short, across three experiments (self-reported gender, 52 females, 26 males, 1 nonbinary), we show that even with perfect luminance matching, unforeseen changes in cognitive state can modulate pupillometric measurements.

Hippocampal pyramidal cells are involved in spatial coding and memory formation. Recent evidence shows that they can be classified according to the origin of their axon, either emerging from the soma (non-AcD for "nonaxon-carrying dendrite") or from a proximal basal dendrite (AcD). We have shown that AcD neurons account for ∼50% of CA1 pyramidal neurons and that they integrate excitatory inputs differently. They are less susceptible to perisomatic inhibition and more strongly recruited during memory-related network oscillations with strong inhibitory activity. Here, we tested whether AcD and non-AcD neurons are differentially engaged during distinct stages of spatial learning. We trained mice of either sex on a spatial memory task (m-maze) and quantified c-Fos expression in CA1 pyramidal neurons at different training stages. AcD and non-AcD cells were distinguished by staining the axon initial segment. Across learning stages, dorsal and medioventral hippocampus showed distinct activation patterns. In dorsal CA1, c-Fos expression shifted from a predominant presence in non-AcD cells at early stages to the increased presence in AcD cells at later stages. In medioventral CA1, AcD neurons showed a transient c-Fos expression peak at intermediate stages of the training, accompanied by a progressive reduction of the percentage of AcD cells over time. This reduction was not observable in the dorsal hippocampus. This suggests region- and cell type-dependent recruitment patterns of CA1 pyramidal cells during learning and indicates that the site of axon origin may undergo structural plasticity. In addition, the findings support functional and structural differentiation along the dorsoventral axis of CA1.

Emotional dysregulation is highly comorbid with sleep disturbances. Sleep is composed of unique physiological states that are reflected by conserved brain oscillations. Though the role of these state-dependent oscillations in cognitive function has been well established, less is known regarding the nature of state-dependent oscillations across brain regions that strongly contribute to emotional function. To characterize these dynamics, we recorded local field potentials simultaneously from multiple cortical and subcortical regions implicated in sleep and emotion regulation and characterized widespread patterns of spectral power and synchrony between brain regions during sleep-wake states in male and female mice. First, we showed that single brain regions encode sleep state, albeit to various degrees of accuracy. We then identified network-based classifiers of sleep based on the combination of features from all recorded brain regions. Spectral power and synchrony from brain networks allowed for automatic, accurate, and rapid discrimination of wake, non-REM sleep (NREM), and rapid eye movement (REM) sleep. When we examined the impact of commonly prescribed sleep-promoting medications on neural dynamics across these regions, we found disparate alterations to both cortical and subcortical activity across all three states. Finally, we found that a stress manipulation that disrupts circadian rhythm in male mice increased sleep fragmentation without altering the underlying average brain dynamics across sleep-wake states. Thus, we characterized state-dependent brain dynamics across regions canonically associated with emotions.

Experimental design is a core competency of scientific training with profound implications for research rigor and reproducibility. Yet, trainees often receive minimal guidance to structure their thinking around experimental design. Metacognition-reflecting on one's own thinking-offers a powerful tool to strengthen reasoning in this process. Here, we present the AiMS framework, which adapts the classic plan-monitor-evaluate cycle of metacognition to the context of experimental design. This framework emphasizes three iterative stages-Awareness, Analysis, and Adaptation-that scaffold reflection on an experimental system defined by its Models, Methods, and Measurements and evaluated through Specificity, Sensitivity, and Stability. We illustrate application of the AiMS framework through an interactive neuroanatomy case study and provide a structured worksheet to guide readers in applying it to their own experiments. We also highlight how the framework can assist researchers in organizing their ideas for research proposals and explore the responsible use of generative AI as a metacognitive partner that supports structured reflection without supplanting original intellectual contributions. The AiMS framework complements other principles and practices of rigor by foregrounding deliberate reasoning about assumptions, vulnerabilities, and trade-offs. Our goal is to provide practical tools that foster rigor, creativity, and adaptability in the design of biological experiments, supporting both trainees and their mentors in cultivating reflective scientific practices.

Novel stimuli can be stressful for individuals with autism spectrum disorders (ASD), though repeated exposure can reduce this effect. In Cntnap2^-/- and Shank3B^+/- mouse models of ASD, novel background odors impaired behavioral target odor recognition but that deficit improved with training. To investigate the neural basis of this improvement, we used wide-field calcium imaging to measure olfactory bulb responses in Cntnap2^-/- and Shank3B^+/- mice and WT mice of either sex. Training with background odors enhanced both behavioral performance and neural discriminability of odor mixtures in both Cntnap2^-/- and Shank3B^+/- as well as WT mice. Naive Cntnap2^-/- and Shank3B^+/- mice showed greater trial-to-trial neural variability than WT mice, but training stabilized neural responses. Critically, training produced a widespread reduction in olfactory bulb responses to background odors in ASD models, but not in WT mice. Thus, despite similar behavioral improvements as WT mice, Cntnap2^-/- and Shank3B^+/- mice relied on a distinct broad suppression of background odor responses to enhance olfactory coding in the presence of background odors.