Frontiers in Behavioral Neuroscience最新文献

Introduction: Air pollution (AP) has been associated with increased risk for multiple neurodevelopmental disorders. As one of the most abundant contaminants of AP, iron (Fe) is critical to brain function, with both deficiencies and excesses leading to potential neurotoxicity. Our prior studies examining the impact of developmental exposures of mice to inhaled Fe (1.0 μg/m³) alone or in conjunction with sulfur dioxide SO₂ (1.31 mg/m³; FeS) from postnatal days (PND) 4-7 and 10-13 (human 3rd trimester brain equivalent period) revealed alterations in brain neurotransmitter levels at PND14 which had generally recovered by PND60, but which were, nevertheless, followed by behavioral impairments. The current study sought to determine whether subsequent behavioral experience, which requires neurochemical mediation, had unmasked residual deficits in neurotransmitter function in response to developmental FeS or Fe inhalation.

Methods: Consequently, levels of brain neurotransmitters and trans-sulfuration markers were measured in mice that had either behavioral experience (BE) or no behavioral experience (NB) at PND 215 (Fe only) or 357 (FeS).

Results: BE itself markedly increased brain neurotransmitter and trans-sulfuration marker levels, particularly in males. These increases were prevented in males in both frontal cortex and striatum by prior developmental FeS exposures. In females, developmental Fe exposure was associated with residual increases particularly in striatal serotonergic function and levels of homocysteine independently of behavioral experience.

Discussion: Collectively, these findings show the ability of behavioral experience to unmask later life residual consequences of developmental exposures to FeS in males and of latent emerging effects of Fe in females. The collective findings may have relevance to later life neurodegenerative diseases and disorders now increasingly associated with air pollution exposures, and also underscore how understanding how various components of air pollution influence brain is critical to regulatory decisions for public health protection.

Introduction: The study aims to evaluate symptomatic differences through psychometric tools comparing patients in the early stages of psychotic development with those exhibiting a more established symptomatology. Our hypothesis was that the early phase in adolescent patients is accompanied by quantitatively and qualitatively distinct symptomatology compared to adults.

Methods: We assessed 116 participants-consisting of 14 to 65 years old patients with psychotic or mood symptoms-using psychometric tools and a clinical interview. The tools explored psychotic, depressive and anxiety dimensions, to provide a multifaceted assessment of the recruited individuals and help at categorizing them into diagnostic subclasses.

Results: We compared patients with psychotic symptoms (early-onset and lifetime) to patients with mood disorders (unipolar depression or bipolar disorder without psychotic symptoms). Psychotic symptoms intensity was significantly higher in the early-onset group compared to the lifetime group and was markedly greater than in the two other groups. It was also observed that the intensity of anxiety and depressive symptoms in the psychosis group were significantly higher in the early-onset subgroup.

Conclusion: Our findings suggest that the clinical presentation of early-onset patients, typically striking in its symptomatology, is reflected by elevated scores on scales not routinely used for psychotic symptoms. This may be attributed to the pervasive destructuring of personality and reality characteristic of early psychotic experiences.

Introduction: Early-onset binge-drinking and biological sex are critical risk factors for the development of cognitive decline and neurodegeneration associated with Alzheimer's disease and related dementias (ADRDs). Recently, we demonstrated that a prior history of binge-drinking during adolescence induces what appears to be latent (>6 months post-drinking) changes in the expression of glutamate receptors and neuropathology markers within brain regions governing working and spatial memory, many of which precede the manifestation of overt cognitive anomalies.

Methods: To determine whether alcohol-induced changes in protein expression manifest within the hippocampus and prefrontal cortex at earlier times post-drinking, we conducted immunoblotting on tissue from mice with a subchronic history of binge-drinking (14 days of 2-h access to 10, 20 and 40% ethanol) during either adolescence or adulthood.

Results: We previously reported that this binge-drinking regimen produces mild, age- and sex-selective, changes in working memory and spatial recall when behavior was assayed starting a 1 or 30 days withdrawal. Here, we provide evidence a subchronic binge-drinking history is sufficient to alter the expression of certain glutamate receptors and ADRD-related proteins during the first few months following drinking cessation. Further, these alcohol-induced protein changes are regionally specific and sex-selective.

Discussion: The present results add to our growing understanding of the long-term consequences of adolescent-onset binge-drinking of potential relevance to understanding individual variability in the cognitive consequences of heavy drinking.

Sex differences are observed in several neurologic and psychiatric disorders. Many aberrant behavioral symptoms can be characterized clinically as either internalizing or externalizing, which tend to manifest disproportionately in females or males, respectively. Stress may precipitate or amplify these behavioral disturbances, which often start in childhood and adolescence but persist into adulthood. Increased understanding of sex differences in stress-induced behavioral changes and their underlying molecular mechanisms is integral to developing better therapeutics specifically tailored to males and females. Here, we highlight the potential of Drosophila melanogaster (D. melanogaster) as a model for the neurobiological study of sex differences in stress-altered behavior. We first review paradigms for stressing D. melanogaster, with an emphasis on social environmental stress. We then introduce behavioral tests that can be used to quantify stress-induced behaviors in flies and note sex differences that emerge in response to stress. Finally, we provide an overview of the known molecular and cellular mechanisms underlying stress-induced behavioral change, with a focus on sex differences and studies incorporating social isolation or crowding.

The current study investigated the influence of testosterone on agonistic behavior and dominance over an opponent before and after adolescence in male Syrian hamsters (Mesocricetus auratus), and tested the hypothesis that shifts in behavioral responsiveness to testosterone occur across adolescent development. We predicted that testosterone-dependent modulation of attacks decreases following puberty, and that flank marking behavior in response to testosterone increases following puberty. Prepubertal (14 days of age) and adult subjects (52-62 days of age) were gonadectomized and immediately implanted with testosterone propionate (TP) or vehicle pellets. Fourteen days later, agonistic behaviors were assessed in a neutral arena with age-matched testosterone-treated opponents. TP treatment increased attacks and dominance over an opponent in prepubertal but not adult males, supporting the hypothesis that testosterone-dependent modulation of aggression decreases following puberty. TP increased flank marking behavior in adults, but failed to increase flank marking in prepubertal subjects, supporting the hypothesized increase in testosterone-dependent modulation of flank marking after puberty. Thus, we provide here evidence that changes in agonistic responses to steroid hormones occur across puberty and adolescence in male rodents, much like the well-established shifts in neuroendocrine and reproductive behavioral responses to steroid hormones that occur pre- to post-pubertally. These findings may have implications for early pubertal timing and increased risk for externalizing symptoms and aggressive behavior in humans.

Like many young mammals, juvenile rats engage in rough-and-tumble play. Play occurs naturally both in wild and laboratory rats, making it a suitable, ethologically relevant behavior to investigate. In the laboratory, rats are typically housed and tested in dyads, despite living in large colonies in the wild. Consequently, when tested in the lab, rats do not have a choice of partners and are instead paired with whomever the researcher selects. Given that both the amount and style of play rats engage in varies considerably depending on the strain of rat being studied, we tested whether rats select play partners based on strain. To do so, juvenile male Long Evans (LE) focal rats (n = 8) were subjected to three play contexts: (1) group play; (2) dyadic play; and (3) social conditioned place preference. During group play, the LE subject rats were given the choice to play with an LE, a Sprague Dawley (SD), or Fischer 344 rat (F344), simultaneously. During dyadic play, focal rats played one-on-one with an LE, SD, or F344 partner. Finally, the rats were conditioned to a context and a social stimulus, with the context either being paired with an LE (preferred stimulus) or F344 (unpreferred stimulus) partner. We found that, when given a choice in a group setting, LE focal rats prefer to play with same-strain partners over both SD and F344 partners. However, when playing under dyadic conditions (i.e., with an assigned partner), LE rats played with each strain equally. Finally, in the socially conditioned place preference test, we found that the focal rats formed preferences for a particular enclosure, but not for the strain. Together, these results suggest that when given a choice, LE rats prefer to play with their own strain, but when they do not have a choice, any strain will do. Given that the testing paradigm can greatly influence the results obtained and the conclusions drawn, our findings highlight the need to consider the research question(s) being asked when determining the most appropriate paradigms to employ.

Social isolation and loneliness have been subject to extensive investigation and discussion by both modern neuroscience and existentialist philosophy. Neuroexistentialism, though controversial, examines how neuroscientific findings inform human existential concerns. In the present discussion, we argue that (1) in the absence of meaningful attributes, typically provided by relationships with objects and others, social isolation and loneliness lead an individual to a pervasive fear of being or the perception of "being-in-the-empty-world" which resembles an existential horror of loneliness; and (2) the pervasiveness of these influences justifies the ubiquity of cerebral responses to both objective and subjective prolonged social disengagement in humans. We also contend that current neuroscientific models of social behaviors, especially within social neuroscience, need to avoid self-affirmative and tautological notions to explain the originality of social connections in human life. By adopting a more integrative and critical approach, these models can better address the complex interplay between social disengagement and their neurological correlates known as the "social brain." This can be accomplished through the establishment of a novel conceptual framework in modern neuroscience to remodel the triad of brain, solitary mind, and society.

Introduction: The renewal effect of extinction describes the reoccurrence of an extinguished response if recall is performed in a context that is not the same as the extinction context. This learning phenomenon is clinically relevant, since it potentially interferes with therapy success for anxiety disorders or phobias. The propensity to show the renewal effect appears to be a stable processing strategy in context-related extinction, associated with higher BOLD activation in hippocampus, ventromedial PFC (vmPFC) and inferior frontal gyrus (IFG) in individuals who show renewal (REN) compared to those who do not (NoREN). However, evidence on a potential relationship between structural properties such as gray matter volume (GMV) in these regions and the propensity to show renewal is lacking.

Methods: In this study, we applied voxel-based morphometry (VBM) to investigate whether individuals with and without a propensity for renewal differ regarding their GMV in extinction-related brain regions, and whether such a difference is linked to the renewal level.

Results: Results revealed differential GMV in REN and NoREN in adjacent subregions of IFG and vmPFC, respectively. Higher GMV in REN was located predominantly in orbital IFG and in BA10 of vmPFC. Higher GMV in NoREN was located predominantly in triangular IFG and in BA 11 of vmPFC. In bilateral anterior cingulate cortex (ACC) and anterior hippocampus, GMV was overall higher in NoREN. In the complete sample, higher GMV in IFG BA 47, vmPFC BA11, bilateral ACC and bilateral anterior hippocampus was associated with less renewal, and partially with a higher error level in extinction learning in a novel context.

Discussion: The findings suggest that higher GMV in several regions active during extinction learning may support a more thorough processing of extinction trials which in turn could be conducive to an extinction recall solely based on recent extinction memory, disregarding context information. In summary, this study provides first-time evidence for a relationship of GMV in of extinction- and renewal-relevant brain regions with behavioral performance during extinction learning and the propensity to show the renewal effect.

Women experience depression at nearly 2-fold higher rates than men, with middle-age during the menopausal transition being particularly vulnerable. Preclinical studies commonly focus on young adult or aged subjects and/or rely upon a few behavioral tasks. Given the highly variable and heterogenous nature of depression, the current study implemented a behavioral battery to assess whether estradiol (E2, endogenously expressed in women and rats) would improve depressive measures using the Research Domain Criteria (RDoC) for negative valence, anhedonia, sociability, and anxiety in early middle-aged, ovariectomized (OVX) female rats. F344-cdf rats were OVX and injected daily with E2 (3 μg/ml, or oil). Behavioral testing began after 14 days of injections, which continued throughout the study. E2 improved the depressive profile when using a composite metric for negative valence (immobility on the forced swim task, FST), anhedonia (duration to initiate grooming following sucrose splash and latency to initiate grooming with sucrose), sociability (time interacting toward a novel conspecific), and novelty-induced anxiety (time spent investigating marbles). Interestingly, FST immobility significantly and positively correlated with sucrose preference to show they were opposingly related: higher immobility on FST corresponded to more sucrose ingested. Also, time spent in a chamber with a novel conspecific was less informative than time directed at the conspecific. Other tasks, such as the marble bury test showed some hoarding behavior. These nuances revealed difficulties in assessing behaviors within and across studies, but overall showed that E2 improved the depressive-like syndrome (DLS) in middle-aged females based upon the RDoC.

Introduction: Inflammation has been implicated as an underlying pathology in negative affect and sleep disruption. Cannabinoids like delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) have demonstrated anti-inflammatory properties. This study aimed to assess if cannabis use altered cytokine concentration and whether inflammatory status moderated the influence of 4 weeks of cannabis use on negative affect and sleep quality in anxious individuals.

Methods: Participants with mild or greater anxiety (n = 147) were assigned to one of three cannabis chemovars (THC + CBD, THC, CBD), asked to consume their products ad libitum for 4 weeks, and were compared to a group of participants with anxiety who did not use cannabis (n = 24). Measures of negative affect (Depression Anxiety and Stress Scale-21: DASS-21), sleep quality (Pittsburgh Sleep Quality Index: PSQI), and plasma cytokine concentrations were measured at Baseline and Week-4. Multilevel modeling assessed if there were group-dependent changes in cytokine concentrations over time, and whether baseline inflammation moderated the association between cannabis use and both negative affect and sleep quality.

Results: There were no group-dependent changes in cytokine concentrations throughout the study (p = 0.12). It was observed that baseline inflammatory state moderated the group-by-time relationship for DASS-21 (p < 0.001) and PSQI (p = 0.04). In both models, chemovars higher in CBD produced more consistent improvements, while THC-associated improvements varied by baseline inflammatory state.

Conclusion: These novel findings suggest that baseline inflammatory status influences the relationship between cannabis use, negative affect, and sleep quality in people with anxiety.