Frontiers in Behavioral Neuroscience最新文献

Introduction: Social isolation, reduced social interaction, and social anhedonia are associated with a range of neuropsychiatric conditions. While the search for novel pharmacological agents to treat social symptoms persists, more precise social behavior measures in pre-clinical animal models are needed to make the most accurate predictions of therapeutic outcomes.

Methods: In the current study, we propose two novel behavioral tasks to measure social motivation in mouse models. We define social motivation as the willingness to exert effort to access a social partner. The first social motivation test, the weighted door task, requires a mouse to push open a one-way, weighted door that increases in weight across successive trials to access a social partner behind the door. The second social motivation test, the ladder task, requires a mouse to climb a ladder that increases in steepness across trials to access a social partner on a platform at the top of the ladder. To validate these tasks, we compared behavioral outcomes across three common inbred strains, C57BL/6J, DBA/2J, and BTBR T + Itpr3 tf /J. Social motivation outcomes were then compared to outcomes in two standard social behavior tests: the three-chamber task and the free dyadic social interaction task.

Results: Following behavioral testing, we found that each strain displayed distinct behavioral responses in social motivation tasks with BTBR mice demonstrating low social motivation, DBA mice demonstrating high social motivation, and C57 mice demonstrating conditionally high social motivation during low effort trials.

Discussion: When combined with standard social behavior testing, our measures provide more detailed social behavior phenotypes unique to each strain. In addition to allowing the creation of more complete social behavior ethograms, these tasks offer advantages as compared to existing conditioning-based behavior tasks measuring social motivation and reward such as the social conditioned place preference task and operant conditioning for social reward. The weighted door and ladder tasks leverage innate exploration behaviors that do not require prior learning which allows for more models, including those with memory, attention, and learning deficits, to be used. These pre-clinical measures of social motivation may prove useful in improving predictions of social behavior outcomes of proposed pharmacological interventions for clinical populations.

Background: Brain dysfunction is a common post-chemotherapy sequela in acute lymphoblastic leukemia (ALL) survivors and is associated with poor academic performance and reduced work ability. The prevention of brain dysfunction in ALL survivors remains a clinical challenge. In this study, we evaluated the preventive effects of probiotics on chemotherapy-induced brain development damage in a preclinical setting.

Methods: The clinical ALL chemotherapy setting was mimicked by intraperitoneally injecting doxorubicin into 4-week-old mice once every 3 days for 2 weeks. Probiotics were administered in the drinking water from the beginning of chemotherapy until adulthood. Behaviors at adulthood were assessed using open field, elevated plus maze, novel object recognition, and Barnes maze tests. Fecal microbiota composition was analyzed using 16S ribosomal RNA (rRNA) gene sequence. Hippocampal neurogenesis was assessed using EdU staining and DCX immunostaining. Synaptic protein expressions were detected using Western blotting.

Results: Early-life chemotherapy induced cognitive dysfunction in adulthood, as demonstrated by impairments in the novel object recognition and Barnes maze tests, but it did not significantly alter anxiety-like behavior in the elevated plus maze. Early-life chemotherapy also induced fecal microbiota dysbiosis both at the end of chemotherapy and in adulthood. Probiotic supplementation alleviated early-life chemotherapy-induced cognitive dysfunction and fecal microbiota dysbiosis in adulthood. In addition, probiotic supplementation also alleviated early-life chemotherapy-induced hippocampal neurogenesis impairments and synaptic protein loss.

Conclusion: Probiotic supplementation can improve early-life chemotherapy-induced brain development impairments in mice by modulating hippocampal neurogenesis.

Introduction: Neonatal hypoxic-ischemic encephalopathy (HIE) is neurological disease caused by the deprivation of oxygen and blood flow to the brain during the developmentally-critical perinatal period. Therapeutic hypothermia (TH) is the standard of care treatment for HIE, though cognitive deficits can persistent throughout life despite treatment. The nature of these deficits, and the impacts of TH and sex are not well understood, and this presents a key barrier in the development of novel therapeutics.

Methods: The goal of this study was to enhance the characterization and measurement of cognitive outcomes with tasks that measure spontaneous behaviors in a rodent models of HIE. Mild-moderate HIE was induced in term-equivalent rats by Vannucci's method and a subset of rats were treated with TH. Cognitive performance was assessed between 6-12 weeks of age.

Results: Hyperactivity and topographical disorientation were observed in HIE rats. Injured rats also spent less time investigating a novel object, suggesting HIE reduced their ability to encode or recognize a familiar object and switch attention to a new object. In a food protection test, injured rats failed to detect an approaching robber rat and protect food items, an indication of impaired attention and egocentric spatial processing. TH treatment resulted in sex-specific attenuation of deficits in attention, learning and skill acquisition, feeding, and processing self-centered spatial cues.

Discussion: These observations highlight the need for deeper understanding of the enduring social and cognitive consequences of neonatal HIE including cases where therapeutic hypothermia was administered. This can pave the way for the development of tailored interventions that enhance the ability of HIE survivors to navigate the complex social and cognitive landscape of adult life.

Introduction: Transcranial infrared laser stimulation (TILS) is a form of photobiomodulation (PBM) using a wavelength of 1064 nm shown to enhance metabolic and hemodynamic activity in the human prefrontal cortex (PFC). Prior studies have shown that when applied to the PFC in the right hemisphere, TILS improves PFC-based memory and learning and sustains attention and mood in healthy adults. However, the temporal duration of PBM mechanisms following a single administration remains poorly understood in humans. The objective of this study was to evaluate the duration of functional connectivity effects of a single administration of TILS to the right anterior PFC during both resting-state and memory-activated conditions over a 5-day period.

Methods: Hemodynamics-derived functional connectivity of the PFC in 12 healthy adults was measured using a 48-channel functional near-infrared spectroscopy (fNIRS) during 5-min resting-state and 2-back memory task activation phases, collected at six time points over a 5-day span. A sham-controlled, within-subject crossover design was employed: all participants received both sham and active TILS in counterbalanced order, with a 4-week washout period between sessions.

Results: Relative to sham, a single administration of TILS significantly modulated PFC functional connectivity during cognitively demanding memory tasks across the 5-day assessment period. No significant effects were observed during resting-state measurements. No adverse effects were reported.

Discussion: These findings suggest that a single administration of TILS can induce functional neuroplasticity in the PFC that persists for several days. The results advance understanding of PBM mechanisms and may inform future interventions aimed at promoting longer-lasting neurocognitive benefits.

The Drosophila Dif gene uses alternative messenger RNA (mRNA) processing to encode two different nuclear factor kappa Bs (NF-κBs). The DifA isoform is a canonical NF-κB transcription factor that is important for activation of the immune response. Our primary interest is the DifB isoform, which is neuron-specific and expressed in the mushroom bodies and antennal lobes of the adult brain. The DifB protein lacks a nuclear localization signal and does not enter the nucleus. Instead, it localizes to the cell body surrounding the nucleus, to axonal-dendritic projections, and to the synapse. DifB is an unusual member of the NF-κB superfamily, as it acts outside the nucleus to modulate behavior. The DifB isoform has been shown to modulate the sensitivity of the adult to sedation by alcohol. Here, we conducted a survey to determine whether the DifB NF-κB is important for other fly behaviors. We observed that a DifB-specific mutation strongly suppresses male courtship. However, despite the expression of DifB in the mushroom bodies, a DifB null allele does not interfere with learning in a learned-suppression-of-phototaxis assay. Finally, both DifA-specific and DifB-specific mutations caused flies to have a circadian long rhythm phenotype, although the circadian phenotype cannot be scored in male DifB mutants because of a sexually dimorphic locomotor defect.

The dorsomedial striatum (DMS) is believed to promote action-outcome associations by integrating cortical and limbic afferents with nigrostriatal dopamine. This functional role for the DMS encompasses reinforcement learning processes traditionally ascribed to the ventral (outcome valuation) and lateral (action-selection) subdivisions of the striatum. Previous studies have shown that DMS dopamine signaling encodes actions and outcomes, often in a lateralized manner (e.g., dopamine release is greater for contralateral actions). To determine how these dynamics evolve with changing action-outcome contingencies, we recorded dopamine axon Ca²⁺ activity in the DMS during a lateralized reversal learning task in mice. Using a miniaturized fluorescence microscope, we found that dopamine axon Ca²⁺ activation in the DMS encoded actions and outcomes with a lateral bias, but only very early in reversal learning, immediately after the action-outcome contingency switch. Specifically, we found that dopamine axon activation during contralateral choices and the rewards associated with those choices were only greater than ipsilateral choices and their rewards in the first session of reversal. Over the course of reversal, reward- and choice-evoked dopamine axon activation subsided for contralateral, but not ipsilateral, choices, resulting in no lateral bias after learning the new action-outcome contingency. Consistent with a causal role for these lateralized dynamics, unilateral optogenetic inhibition of the nigrostriatal dopamine pathway impaired contralateral reversal by reducing "win-stay" responses. However, this deficit was transient, occurring only during the first reversal session. Our results suggest that dopamine signaling in the DMS facilitates the exploration of new actions, specifically at the specific moment the previous action-outcome contingency becomes conflicted. In our lateralized reversal learning task, this facilitation was particularly important when the new action and resulting outcome were contralateral to the recorded hemisphere. These findings advance our understanding of how the DMS carries out its ascribed role in action-outcome learning.

Introduction: Food competition is a major cost to group living. Resources vary in quality, distribution, and handling times, exerting differing competitive regimes and varied effects on individual food intake depending on dominance rank.

Methods: To investigate this interplay and the tipping points between purely contest and purely scramble scenarios, we conducted a field experiment on wild vervet monkeys (Chlorocebus pygerythrus), a species with linear, nepotistic intragroup dominance hierarchies. We baited a multi-destination foraging array with a mixture of clumped, preferred and less clumped, less preferred rewards to observe how individuals' foraging decisions and route choices were affected by the presence and proximity of competitors. In contrast to previous experiments conducted with this group, rewards had minimal handling times and greater quantities to create a mix of scramble and contest competition.

Results: We found that neither an individual's dominance rank nor the frequency with which they faced competition from a dominant competitor significantly affected their overall foraging success, suggesting that we were successful in invoking scramble competition. All individuals, regardless of rank, generally chose to prioritize the best reward at the cost of a less efficient route and increased travel time. Nonetheless, encountering dominant competitors in a higher proportion of trials made focal individuals more likely to begin trials at the nearest, less preferred reward, rather than face contest competition for the preferred, more distant platform.

Discussion: Our findings suggest that though greater scramble competition minimizes differences in food intake, risk avoidance still exerts powerful effects on the foraging route choices of those experiencing competition.

Introduction: Stressful life events can trigger the initiation of cocaine use, facilitate the transition to a cocaine-use disorder (CUD), and precipitate relapse. Evidence suggests that women progress more rapidly to a CUD than men. Thus, the influence of stressful life events on CUD development may differ by sex, contributing to the enhanced vulnerability seen among females. In this work, we provide a comprehensive (non-systematic) review of clinical and preclinical studies comparing the effects of cocaine and its modulation by stress in both sexes.

Methods: We performed a search of the PubMed database (1986-2025) in which we combined the keywords "cocaine" and "stress" with "sex differences" or "female rat" or "female mice" or "women." We then read the abstracts of the search results to select potentially relevant studies, which we read in full to determine if they fulfilled our criteria and to extract the relevant information.

Results: Sex is often overlooked as a biological variable in preclinical and clinical research. The results of clinical studies indicate the existence of sex differences in the response to stress among individuals with CUD. Preclinical studies strongly suggest that female rodents are more vulnerable to developing addiction-like features than male rodents, particularly in the self-administration paradigm. Furthermore, exposure to stress appears to amplify the effects of cocaine, especially in females.

Discussion: There is growing evidence that women and female rodents are more vulnerable to the behavioral and neurochemical changes that characterize cocaine addiction. The influence of sex should be considered in research and in the selection of strategies for preventing and treating CUD, including those targeting stress reduction.

Objective: Teacher stress is a global concern with significant consequences for health, performance, and educational quality. While most studies address stress as a harmful phenomenon, emerging evidence suggests that an individual's mindset toward stress can influence both psychological and physiological outcomes. This study investigated whether a brief video-based mindset intervention could alter stress perception and modulate biological stress markers among public school teachers in Brazil.

Methods: A randomized controlled trial was conducted with 63 teachers allocated into intervention (n = 32) and control (n = 31) groups. The intervention group received an 8-days series of short educational videos developed by Stanford University's Mind and Body Lab, designed to promote a growth-oriented stress mindset. Measures included the Stress Mindset Measure (SMM), Perceived Stress Scale (PSS-10), Stroop Color Task, and salivary biomarkers (cortisol and DHEA-S). Data were collected at baseline, post-intervention, and 30-days follow-up. Analyses included repeated measures ANOVA and t-tests.

Results: The intervention significantly improved stress mindset scores immediately after the intervention and at follow-up (p < 0.001; ε² = 0.664), with no change in the control group. Cortisol concentrations decreased significantly in the intervention group post-intervention (p = 0.004; ε² = 0.262), though the effect was not maintained after 30 days. No significant changes were observed in DHEA-S levels. Additionally, cognitive performance on the Stroop incongruent task improved significantly in the intervention group (p = 0.003; d = 0.565), suggesting enhanced executive functioning under stress.

Discussion: The findings support the effectiveness of a brief, low-cost intervention in shifting stress mindsets and producing acute physiological and cognitive benefits. However, the transient nature of the hormonal response underscores the need for sustained or complementary strategies to reinforce long-term stress resilience. This study highlights the value of mindset-based approaches in educational settings and their potential for improving teacher well-being through psychoneuroendocrinological mechanisms.

Introduction: Extinction learning of conditioned fear behavior has been used as a translational model to study human fear-, anxiety-, trauma-, and stressor-related disorders and their underlying neurobiology in animal models because the underlying neural processes of extinction learning are fundamental to the most effective clinical interventions for these disorders. Specifically, extinction-based prolonged exposure therapy is the first-line, gold-standard, cognitive behavioral treatment for fear-, trauma-, stressor-, and anxiety-based disorders. However, the ways that parametric differences in methodologies alter extinction learning are still not well understood.

Methods: Therefore, in the current study, we altered the number of days on which an equal number of extinction trials were presented in an extinction of conditioned fear learning-paradigm. As part of this paradigm, we employed fear-potentiated startle as a primary outcome measure of fear responses in adult, male rats. One group received 120 massed extinction trials in 1 day, a second group received 120 extinction trials across 2 days, and a final group received 120 extinction trials spaced across 4 days. We hypothesized that a greater number of days of extinction training would lead to improved extinction retention.

Results: We found minimal differences between groups on the final test of extinction retention, although increased fear behaviors were observed at the start of the second day of extinction training in the 2-day group.

Discussion: These findings have implications with respect to the flexibility of fear extinction methodologies employed as well as to how data generated from chosen paradigms is interpreted.