Frontiers in Behavioral Neuroscience最新文献

Sex differences are well-documented in the prevalence of psychiatric disorders, with anxiety and stress-related conditions more common in women. Growing evidence highlights the role of sex hormones, particularly estradiol (E2), and its receptor mechanisms as contributing factors to this disparity. Estrogen exerts its effects through three main receptors: estrogen receptor alpha (ERα), estrogen receptor beta (ERβ), and the G protein-coupled estrogen receptor (GPER). While the classical receptors ERα and ERβ have been widely studied in the context of fear and anxiety, the role of GPER remains less understood. Moreover, estrogen receptors themselves may be sexually dimorphic, adding complexity to their functional roles. Preclinical research has been valuable in advancing our understanding of these mechanisms; therefore, this review mostly focuses on findings from rodent studies. Here we discuss the influence of sex and E2 on anxiety and fear-related behavior, highlight emerging research on sex differences in GPER modulation of fear and anxiety in mice, rats, and humans, and explore GPER as a potential therapeutic target for anxiety and stress-related disorders.

Introduction: The study of social behavior in mice has grown increasingly relevant for unraveling associated brain circuits and advancing the development of treatments for psychiatric symptoms involving social withdrawal or social anxiety. However, a data-driven understanding of behavior and its modulation in solitary and social contexts is lacking.

Methods: In this study, we employed motion sequencing ("MoSeq") to decompose mouse behaviors into discrete units ("syllables") and investigate whether-and how-the behavioral repertoire differs between solitary and dyadic (social) settings.

Results: Our results reveal that social context significantly modulates a minority (25%) of syllables, containing predominantly stationary and undirected behaviors. Notably, these changes are associated with spatial proximity to another mouse rather than active social contact. Interestingly, a network analysis of syllable transitions shows that context-sensitive syllables exhibit altered network influence, independent of the number of connected syllables, suggesting a regulatory role. Furthermore, syllable composition changes significantly during social contact events with two distinct sequence families governing approach and withdrawal behaviors. However, no unique syllable sequences mapped to specific social interactions.

Discussion: Overall, our findings suggest that a subset of syllables drives contextual behavioral adaptation in female and male mice, potentially facilitating transitions within the broader behavioral repertoire. This highlights the utility of MoSeq in dissecting nuanced, context-dependent behavioral dynamics.

Krabbe disease (KD), also known as globoid cell leukodystrophy, is a rare autosomal recessive neurodegenerative disorder caused by pathogenic variants in the GALC gene. While infantile-onset KD is prevalent globally, adult-onset KD is frequently presented in East Asian populations and typically manifests with progressive spastic paraparesis. We herein report a unique case of a 28-years-old male who initially presented with generalized tonic-clonic seizures, rather than the classic gait disturbance. Brain MRI revealed symmetrical white matter lesions and early cortical involvement. Genetic testing revealed compound heterozygous GALC variants (c.908C > T/p.Ser303Phe and c.136G > T/p.Asp46Tyr). Subsequent enzyme assays confirmed low galactocerebrosidase activity. This case broadens the clinical spectrum of adult-onset KD and highlights the importance of considering KD in the differential diagnosis of adult epilepsy with progressive neurological symptoms.

Introduction: Adolescence shapes adaptive adult behaviors. It is characterized by increased responsiveness to socially salient stimuli and heightened sensitivity to rewards in peer settings. The particular importance of social context during adolescence indicates that neural circuits responsible for social reward may develop along a different trajectory from those involved in non-social reward processing. However, this remains largely unexplored, as much of the existing research tends to focus on a single reward type, a specific age group of adolescents, or a single sex, thereby limiting a comprehensive understanding of how reward processing evolves across development.

Methods: Here, we investigated how social, cocaine, and palatable food reward sensitivity is expressed in female and male C57BL/6 mice across early- (pubertal onset), mid- (peripubertal phase), and late- (sexual maturity) adolescence, compared to adults. We examined how these different rewards become associated with environmental contexts across developmental stages using the conditioned place preference (CPP) paradigm, a fundamental method for evaluating the motivational properties of stimuli.

Results: We found that adolescent mice exhibited a lower preference for social and palatable food conditioned contexts, while cocaine CPP was not significantly affected by age. Comparisons across CPP tasks confirmed that age, rather than reward type or sex, was the primary factor influencing the magnitude of CPP. Overall, mid- and late-adolescent mice showed reduced mean CPP, with mid-adolescents exhibiting significantly lower odds of expressing a conditioned preference relative to adults.

Discussion: These findings challenge the prevailing assumption that adolescent reward sensitivity universally enhances reward-context learning. Instead, we propose that the attenuated CPP observed in adolescence reflects lower reward sensitivity in emotionally neutral conditions, rather than deficits in associative learning or increased novelty seeking. Our results highlight how developmental stage influences reward-related behaviors and underscore the need for age- and sex-specific analyses in behavioral studies.

Oscillatory activity is thought to coordinate neural computations across brain regions, and theta oscillations are critical for learning and memory. Because respiration-related oscillations (RROs) in rodents can be identified in the prefrontal cortex (PFC) and the hippocampus in addition to canonical theta oscillations, we asked whether odor-cued working memory may be supported by both of these two oscillations. We first confirmed that RROs were propagated to the hippocampus and PFC and that RRO frequency spans a broad range that partially overlaps with canonical theta frequency. During all task phases, we found coherence between PFC and hippocampus at the RRO frequency, irrespective of whether RROs and canonical theta oscillations overlapped or differed in frequency. In parallel, there was also high coherence across PFC and hippocampus at theta frequency, except that the coupling at theta was weakest during odor sampling. Therefore, long-range coordination between brain regions occurs at more than one oscillation frequency in a working memory task, but the two types of oscillations did not show evidence of conjunctively supporting working memory.

Deep brain stimulation of the nucleus accumbens (NAc-DBS) has been shown to ameliorate depressive-like behaviors. However, the underlying mechanisms of action remain elusive. We aimed to investigate the impact of NAc-DBS on synaptic spine alterations in hippocampus in a depression mice model and unveil the possible signal pathway mediating such effects. The experimental protocol involved exposing adult mice to chronic unpredictable mild stress (CUMS) with or without NAc-DBS. Behavioral assessments were performed to evaluate the impact of NAc-DBS on emotional alterations. Local field potential (LFP) recordings were employed to examine the hippocampal neuronal activity in awake mice. Golgi-Cox staining was applied to quantify modifications in dendritic spine density. Additionally, hippocampal protein expression of postsynaptic density protein-95 (PSD-95), brain-derived neurotrophic factor (BDNF), and the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway were analyzed. Results indicate that CUMS mice exhibited apparent depressive-like behaviors, concomitant with reduced hippocampal high gamma oscillation power and synaptic spine density. In addition, CUMS reduced the expression level of PSD-95 and BDNF in mice hippocampus, as well as phosphorylated AKT and mTOR protein. The study revealed that NAc-DBS could attenuate depression-like behaviors, restore high gamma oscillation power and enhance synaptic spine density, potentially by increasing BDNF protein expression level and activating AKT/mTOR signaling pathway. Furthermore, Rapamycin, a potent and specific mTOR inhibitor, was found to moderate the effects of NAc-DBS. These findings suggest that NAc-DBS could enhance synaptic spine density via AKT/mTOR/BDNF signal pathway, which may partially underline its potential antidepressant effects in CUMS induced depressive models.

Behavioral neuroscience generally conceives of habits as under stimulus-response control, and distinguishes habits from goal-directed behavior based on their insensitivity to outcome value (features of automaticity). However, the everyday meaning of "bad habits" is applied primarily to behaviors that are compelling, in part, because of their anticipated outcome value. In particular, commonly identified bad habits (e.g., overuse of social media, overeating, smoking) are repeated behaviors that yield appealing immediate outcomes, but at a greater longer term cost ("temptations"). We begin by evaluating the role of both automaticity and temptation in the maintenance of bad habits. Next we focus on how framing effects can be used to shift the balance of motivation away from immediate and/or toward delayed outcome value, including a partial summary of what is known about the neural substrates that mediate such shifts. We pay particular attention to the way frames can promote replacing bad habits with good habits through emphasizing the connection between specific choices and general policy preferences.

The novel tank diving test (NTT) is a widely used behavioral assay for evaluating anxiety-like behaviors in zebrafish; however, results often exhibit considerable variability across different experimental settings. In this study, we systematically analyzed various methodological factors influencing the outcomes of NTT and introduced refinements to enhance its reliability and reproducibility. We optimized the detection parameters for region entry and freezing behavior using logistic regression analysis, significantly reducing false-positive classifications caused by tracking artifacts. The impact of pre-test stress conditions-restraint and darkness-was assessed, demonstrating that restraint effectively decreased the variability in behavioral parameters, such as latency to enter the top half (LTTH) of the tank and frequency of entries (FE). Conversely, combining darkness with restraint induced abnormal behaviors, limiting utility of the test. The effects of temperature were also rigorously evaluated, revealing that even subtle deviations within 3 °C of the standard temperature of 26.5 °C significantly affected behavioral variability, and 26.5 °C was optimal for reliable outcomes. Furthermore, we demonstrated that net-chasing during fish handling significantly increased the freezing time, suggesting the adoption of funnel-based transfers to reduce stress artifacts. Finally, behavioral patterns during stable test conditions followed a Poisson process, enabling the estimation of optimal test durations. Overall, our proposed refinements help establish a standardized, robust NTT protocol that minimizes variability and enhances the assay's sensitivity and reproducibility to investigate anxiety behavior in zebrafish.

Introduction: Opioid use disorder (OUD) is a chronic relapsing condition caused by prolonged opioid exposure, which triggers adaptive changes in the brain. These changes make it challenging to control or abstain from consuming, and significantly increase the risk of relapse. While the physical symptoms of withdrawal typically resolve within a few days, extended abstinence is frequently accompanied by the progressive development of emotional disturbances. Additionally, abstinent individuals often report social disengagement, or even social isolation that worsen the condition and participates in the development of comorbidities. These disturbances are similarly observed in murine models of opioid abstinence.

Methods: However, traditional methods for assessing social deficits in rodents often rely on simplistic paradigms with limited behavioral metrics. Here, we utilized a well-established model of morphine administration followed by protracted abstinence, combined with the Live Mouse Tracker (LMT) system. Using the real-time video-based automated LMT system, we conducted longitudinal recordings of social behaviors over a 4-week period of morphine abstinence, during repeated social interaction sessions.

Results: The use of this method, offering an unbiased and precise behavioral characterization of social investigation between freely-moving male mice, revealed that while motor and activity-related disruptions emerge and resolve quickly immediately following the onset of abstinence, social deficits progressively intensify over time, reaching their peak 3 weeks after the final morphine administration. Additionally, the LMT provided detailed insights into subtle behavioral changes throughout the course of abstinence and within individual but also that early deficits in explorations and social interactions might serve as predictor for the severity of the late social deficits.

Discussion: These results point out the need to improve and implement unbiased tracking methods for a deeper and refined understanding of rodent behaviors modeling psychiatric conditions.

Motor learning is supported by both explicit and implicit processes. A central question in the field of motor control is how these two processes interact and, critically, how each process can be assessed in an unbiased manner. In this perspective paper, we propose that the autonomic nervous system (ANS) offers an informative window into explicit cognitive processes during motor learning. We first briefly review studies outside the motor learning domain, where ANS activity has been linked to internal cognitive states such as surprise and uncertainty. We then discuss how these ANS-related states can be leveraged to assess the manifestation and influence of explicit processes during motor learning, as well as to explore cognitive computations that may involve central ANS activity, including contextual inference.