Pub Date : 2024-09-18DOI: 10.3389/fnbeh.2024.1455478
Alyssa R. Kniffin, Lisa A. Briand
Disruptions in glutamate homeostasis within the mesolimbic reward circuitry may play a role in the pathophysiology of various reward related disorders such as major depressive disorders, anxiety, and substance use disorders. Clear sex differences have emerged in the rates and symptom severity of these disorders which may result from differing underlying mechanisms of glutamatergic signaling. Indeed, preclinical models have begun to uncover baseline sex differences throughout the brain in glutamate transmission and synaptic plasticity. Glutamatergic synaptic strength can be assessed by looking at morphological features of glutamatergic neurons including spine size, spine density, and dendritic branching. Likewise, electrophysiology studies evaluate properties of glutamatergic neurons to provide information of their functional capacity. In combination with measures of glutamatergic transmission, synaptic plasticity can be evaluated using protocols that induce long-term potentiation or long-term depression. This review will consider preclinical rodent literature directly comparing glutamatergic transmission and plasticity in reward related regions of males and females. Additionally, we will suggest which regions are exhibiting evidence for sexually dimorphic mechanisms, convergent mechanisms, or no sex differences in glutamatergic transmission and plasticity and highlight gaps in the literature for future investigation.
{"title":"Sex differences in glutamate transmission and plasticity in reward related regions","authors":"Alyssa R. Kniffin, Lisa A. Briand","doi":"10.3389/fnbeh.2024.1455478","DOIUrl":"https://doi.org/10.3389/fnbeh.2024.1455478","url":null,"abstract":"Disruptions in glutamate homeostasis within the mesolimbic reward circuitry may play a role in the pathophysiology of various reward related disorders such as major depressive disorders, anxiety, and substance use disorders. Clear sex differences have emerged in the rates and symptom severity of these disorders which may result from differing underlying mechanisms of glutamatergic signaling. Indeed, preclinical models have begun to uncover baseline sex differences throughout the brain in glutamate transmission and synaptic plasticity. Glutamatergic synaptic strength can be assessed by looking at morphological features of glutamatergic neurons including spine size, spine density, and dendritic branching. Likewise, electrophysiology studies evaluate properties of glutamatergic neurons to provide information of their functional capacity. In combination with measures of glutamatergic transmission, synaptic plasticity can be evaluated using protocols that induce long-term potentiation or long-term depression. This review will consider preclinical rodent literature directly comparing glutamatergic transmission and plasticity in reward related regions of males and females. Additionally, we will suggest which regions are exhibiting evidence for sexually dimorphic mechanisms, convergent mechanisms, or no sex differences in glutamatergic transmission and plasticity and highlight gaps in the literature for future investigation.","PeriodicalId":12368,"journal":{"name":"Frontiers in Behavioral Neuroscience","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142269529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-18DOI: 10.3389/fnbeh.2024.1418577
Nicholas Vidas-Guscic, Elisabeth Jonckers, Johan Van Audekerke, Jasmien Orije, Julie Hamaide, Gaurav Majumdar, Laurence Henry, Martine Hausberger, Marleen Verhoye, Annemie Van der Linden
The present study aims to investigate whether begging calls elicit specific auditory responses in non-parenting birds, whether these responses are influenced by the hormonal status of the bird, and whether they reflect biparental care for offspring in the European starling (Sturnus vulgaris). An fMRI experiment was conducted to expose non-parenting male and female European starlings to recordings of conspecific nestling begging calls during both artificially induced breeding and non-breeding seasons. This response was compared with their reaction to conspecific individual warbling song motifs and artificial pure tones, serving as social species-specific and artificial control stimuli, respectively. Our findings reveal that begging calls evoke a response in non-parenting male and female starlings, with significantly higher responsiveness observed in the right Field L and the Caudomedial Nidopallium (NCM), regardless of season or sex. Moreover, a significant seasonal variation in auditory brain responses was elicited in both sexes exclusively by begging calls, not by the applied control stimuli, within a ventral midsagittal region of NCM. This heightened response to begging calls, even in non-parenting birds, in the right primary auditory system (Field L), and the photoperiod induced hormonal neuromodulation of auditory responses to offspring’s begging calls in the secondary auditory system (NCM), bears resemblance to mammalian responses to hunger calls. This suggests a convergent evolution aimed at facilitating swift adult responses to such calls crucial for offspring survival.
{"title":"Adult auditory brain responses to nestling begging calls in seasonal songbirds: an fMRI study in non-parenting male and female starlings (Sturnus vulgaris)","authors":"Nicholas Vidas-Guscic, Elisabeth Jonckers, Johan Van Audekerke, Jasmien Orije, Julie Hamaide, Gaurav Majumdar, Laurence Henry, Martine Hausberger, Marleen Verhoye, Annemie Van der Linden","doi":"10.3389/fnbeh.2024.1418577","DOIUrl":"https://doi.org/10.3389/fnbeh.2024.1418577","url":null,"abstract":"The present study aims to investigate whether begging calls elicit specific auditory responses in non-parenting birds, whether these responses are influenced by the hormonal status of the bird, and whether they reflect biparental care for offspring in the European starling (<jats:italic>Sturnus vulgaris</jats:italic>). An fMRI experiment was conducted to expose non-parenting male and female European starlings to recordings of conspecific nestling begging calls during both artificially induced breeding and non-breeding seasons. This response was compared with their reaction to conspecific individual warbling song motifs and artificial pure tones, serving as social species-specific and artificial control stimuli, respectively. Our findings reveal that begging calls evoke a response in non-parenting male and female starlings, with significantly higher responsiveness observed in the right Field L and the Caudomedial Nidopallium (NCM), regardless of season or sex. Moreover, a significant seasonal variation in auditory brain responses was elicited in both sexes exclusively by begging calls, not by the applied control stimuli, within a ventral midsagittal region of NCM. This heightened response to begging calls, even in non-parenting birds, in the right primary auditory system (Field L), and the photoperiod induced hormonal neuromodulation of auditory responses to offspring’s begging calls in the secondary auditory system (NCM), bears resemblance to mammalian responses to hunger calls. This suggests a convergent evolution aimed at facilitating swift adult responses to such calls crucial for offspring survival.","PeriodicalId":12368,"journal":{"name":"Frontiers in Behavioral Neuroscience","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142266487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-18DOI: 10.3389/fnbeh.2024.1450540
Marion Rivalan, Lucille Alonso, Valentina Mosienko, Patrik Bey, Alexia Hyde, Michael Bader, York Winter, Natalia Alenina
Aggression is an adaptive social behavior crucial for the stability and prosperity of social groups. When uncontrolled, aggression leads to pathological violence that disrupts group structure and individual wellbeing. The comorbidity of uncontrolled aggression across different psychopathologies makes it a potential endophenotype of mental disorders with the same neurobiological substrates. Serotonin plays a critical role in regulating impulsive and aggressive behaviors. Mice lacking in brain serotonin, due to the ablation of tryptophan hydroxylase 2 (TPH2), the rate-limiting enzyme in serotonin synthesis, could serve as a potential model for studying pathological aggression. Home cage monitoring allows for the continuous observation and quantification of social and non-social behaviors in group-housed, freely-moving mice. Using an ethological approach, we investigated the impact of central serotonin ablation on the everyday expression of social and non-social behaviors and their correlations in undisturbed, group-living Tph2-deficient and wildtype mice. By training a machine learning algorithm on behavioral time series, “allogrooming”, “struggling at feeder”, and “eating” emerged as key behaviors dissociating one genotype from the other. Although Tph2-deficient mice exhibited characteristics of pathological aggression and reduced communication compared to wildtype animals, they still demonstrated affiliative huddle behaviors to normal levels. Altogether, such a distinct and dynamic phenotype of Tph2-deficient mice influenced the group's structure and the subsequent development of its hierarchical organization. These aspects were analyzed using social network analysis and the Glicko rating methods. This study demonstrates the importance of the ethological approach for understanding the global impact of pathological aggression on various aspects of life, both at the individual and group levels. Home cage monitoring allows the observation of the natural behaviors of mice in a semi-natural habitat, providing an accurate representation of real-world phenomena and pathological mechanisms. The results of this study provide insights into the neurobiological substrate of pathological aggression and its potential role in complex brain disorders.
{"title":"Serotonin drives aggression and social behaviors of laboratory male mice in a semi-natural environment","authors":"Marion Rivalan, Lucille Alonso, Valentina Mosienko, Patrik Bey, Alexia Hyde, Michael Bader, York Winter, Natalia Alenina","doi":"10.3389/fnbeh.2024.1450540","DOIUrl":"https://doi.org/10.3389/fnbeh.2024.1450540","url":null,"abstract":"Aggression is an adaptive social behavior crucial for the stability and prosperity of social groups. When uncontrolled, aggression leads to pathological violence that disrupts group structure and individual wellbeing. The comorbidity of uncontrolled aggression across different psychopathologies makes it a potential endophenotype of mental disorders with the same neurobiological substrates. Serotonin plays a critical role in regulating impulsive and aggressive behaviors. Mice lacking in brain serotonin, due to the ablation of tryptophan hydroxylase 2 (TPH2), the rate-limiting enzyme in serotonin synthesis, could serve as a potential model for studying pathological aggression. Home cage monitoring allows for the continuous observation and quantification of social and non-social behaviors in group-housed, freely-moving mice. Using an ethological approach, we investigated the impact of central serotonin ablation on the everyday expression of social and non-social behaviors and their correlations in undisturbed, group-living <jats:italic>Tph2</jats:italic>-deficient and wildtype mice. By training a machine learning algorithm on behavioral time series, “allogrooming”, “struggling at feeder”, and “eating” emerged as key behaviors dissociating one genotype from the other. Although <jats:italic>Tph2</jats:italic>-deficient mice exhibited characteristics of pathological aggression and reduced communication compared to wildtype animals, they still demonstrated affiliative huddle behaviors to normal levels. Altogether, such a distinct and dynamic phenotype of <jats:italic>Tph2</jats:italic>-deficient mice influenced the group's structure and the subsequent development of its hierarchical organization. These aspects were analyzed using social network analysis and the Glicko rating methods. This study demonstrates the importance of the ethological approach for understanding the global impact of pathological aggression on various aspects of life, both at the individual and group levels. Home cage monitoring allows the observation of the natural behaviors of mice in a semi-natural habitat, providing an accurate representation of real-world phenomena and pathological mechanisms. The results of this study provide insights into the neurobiological substrate of pathological aggression and its potential role in complex brain disorders.","PeriodicalId":12368,"journal":{"name":"Frontiers in Behavioral Neuroscience","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142266488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-12DOI: 10.3389/fnbeh.2024.1445184
Christopher A. Guevara, Kumayl Alloo, Swati Gupta, Romario Thomas, Pamela del Valle, Alexandra R. Magee, Deanna L. Benson, George W. Huntley
Anxiety is a psychiatric non-motor symptom of Parkinson’s that can appear in the prodromal period, prior to significant loss of midbrain dopamine neurons and motor symptoms. Parkinson’s-related anxiety affects females more than males, despite the greater prevalence of Parkinson’s in males. How stress, anxiety and Parkinson’s are related and the basis for a sex-specific impact of stress in Parkinson’s are not clear. We addressed this using young adult male and female mice carrying a G2019S knockin mutation of leucine-rich repeat kinase 2 (Lrrk2G2019S) and Lrrk2WT control mice. In humans, LRRK2G2019S significantly elevates the risk of late-onset Parkinson’s. To assess within-sex differences between Lrrk2G2019S and control mice in stress-induced anxiety-like behaviors in young adulthood, we used a within-subject design whereby Lrrk2G2019S and Lrrk2WT control mice underwent tests of anxiety-like behaviors before (baseline) and following a 28 day (d) variable stress paradigm. There were no differences in behavioral measures between genotypes in males or females at baseline, indicating that the mutation alone does not produce anxiety-like responses. Following chronic stress, male Lrrk2G2019S mice were affected similarly to male wildtypes except for novelty-suppressed feeding, where stress had no impact on Lrrk2G2019S mice while significantly increasing latency to feed in Lrrk2WT control mice. Female Lrrk2G2019S mice were impacted by chronic stress similarly to wildtype females across all behavioral measures. Subsequent post-stress analyses compared cFos immunolabeling-based cellular activity patterns across several stress-relevant brain regions. The density of cFos-activated neurons across brain regions in both male and female Lrrk2G2019S mice was generally lower compared to stressed Lrrk2WT mice, except for the nucleus accumbens of male Lrrk2G2019S mice, where cFos-labeled cell density was significantly higher than all other groups. Together, these data suggest that the Lrrk2G2019S mutation differentially impacts anxiety-like behavioral responses to chronic stress in males and females that may reflect sex-specific adaptations observed in circuit activation patterns in some, but not all stress-related brain regions.
{"title":"Parkinson’s LRRK2-G2019S risk gene mutation drives sex-specific behavioral and cellular adaptations to chronic variable stress","authors":"Christopher A. Guevara, Kumayl Alloo, Swati Gupta, Romario Thomas, Pamela del Valle, Alexandra R. Magee, Deanna L. Benson, George W. Huntley","doi":"10.3389/fnbeh.2024.1445184","DOIUrl":"https://doi.org/10.3389/fnbeh.2024.1445184","url":null,"abstract":"Anxiety is a psychiatric non-motor symptom of Parkinson’s that can appear in the prodromal period, prior to significant loss of midbrain dopamine neurons and motor symptoms. Parkinson’s-related anxiety affects females more than males, despite the greater prevalence of Parkinson’s in males. How stress, anxiety and Parkinson’s are related and the basis for a sex-specific impact of stress in Parkinson’s are not clear. We addressed this using young adult male and female mice carrying a G2019S knockin mutation of leucine-rich repeat kinase 2 (<jats:italic>Lrrk2</jats:italic><jats:sup>G2019S</jats:sup>) and <jats:italic>Lrrk2</jats:italic><jats:sup>WT</jats:sup> control mice. In humans, <jats:italic>LRRK2</jats:italic><jats:sup>G2019S</jats:sup> significantly elevates the risk of late-onset Parkinson’s. To assess within-sex differences between <jats:italic>Lrrk2</jats:italic><jats:sup>G2019S</jats:sup> and control mice in stress-induced anxiety-like behaviors in young adulthood, we used a within-subject design whereby <jats:italic>Lrrk2</jats:italic><jats:sup>G2019S</jats:sup> and <jats:italic>Lrrk2</jats:italic><jats:sup>WT</jats:sup> control mice underwent tests of anxiety-like behaviors before (baseline) and following a 28 day (d) variable stress paradigm. There were no differences in behavioral measures between genotypes in males or females at baseline, indicating that the mutation alone does not produce anxiety-like responses. Following chronic stress, male <jats:italic>Lrrk2</jats:italic><jats:sup>G2019S</jats:sup> mice were affected similarly to male wildtypes except for novelty-suppressed feeding, where stress had no impact on <jats:italic>Lrrk2</jats:italic><jats:sup>G2019S</jats:sup> mice while significantly increasing latency to feed in <jats:italic>Lrrk2</jats:italic><jats:sup>WT</jats:sup> control mice. Female <jats:italic>Lrrk2</jats:italic><jats:sup>G2019S</jats:sup> mice were impacted by chronic stress similarly to wildtype females across all behavioral measures. Subsequent post-stress analyses compared cFos immunolabeling-based cellular activity patterns across several stress-relevant brain regions. The density of cFos-activated neurons across brain regions in both male and female <jats:italic>Lrrk2</jats:italic><jats:sup>G2019S</jats:sup> mice was generally lower compared to stressed <jats:italic>Lrrk2</jats:italic><jats:sup>WT</jats:sup> mice, except for the nucleus accumbens of male <jats:italic>Lrrk2</jats:italic><jats:sup>G2019S</jats:sup> mice, where cFos-labeled cell density was significantly higher than all other groups. Together, these data suggest that the <jats:italic>Lrrk2</jats:italic><jats:sup>G2019S</jats:sup> mutation differentially impacts anxiety-like behavioral responses to chronic stress in males and females that may reflect sex-specific adaptations observed in circuit activation patterns in some, but not all stress-related brain regions.","PeriodicalId":12368,"journal":{"name":"Frontiers in Behavioral Neuroscience","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142180016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The objective of this study was to explore the impact of different persuasive strategies, as delineated in the Elaboration Likelihood Model (ELM), on attentional processes using event-related potentials (ERPs).IntroductionThis study aimed to investigate how central versus peripheral persuasion methods, delivered through rational and emotional persuasion strategies, influence cognitive engagement and information processing during visual search tasks.MethodsParticipants were allocated into four groups based on the media type (video vs. text) and the persuasion route (central vs. peripheral). The early and late stages of attentional processing were examined through the N1, P2, and P3 ERP components.ResultsThe results demonstrated a pronounced N1 amplitude in response to text-based peripheral persuasion, indicating enhanced early attentional engagement. Additionally, parallel search tasks revealed a larger P3 amplitude for central versus peripheral routes, suggesting significant cognitive resource allocation during tasks requiring higher attention.DiscussionThese findings underscore the nuanced role of persuasive strategies in modulating attentional resources and cognitive processing. The study offers insights into designing more effective communication messages and highlights the potential for tailored persuasion approaches to influence audience engagement and information processing, with implications for public health campaigns and beyond.
{"title":"Unveiling the influence of persuasion strategies on cognitive engagement: an ERPs study on attentional search","authors":"Lichao Xiu, Xuejiao Chen, Lulu Mao, Enyu Zhang, Guoming Yu","doi":"10.3389/fnbeh.2024.1302770","DOIUrl":"https://doi.org/10.3389/fnbeh.2024.1302770","url":null,"abstract":"The objective of this study was to explore the impact of different persuasive strategies, as delineated in the Elaboration Likelihood Model (ELM), on attentional processes using event-related potentials (ERPs).IntroductionThis study aimed to investigate how central versus peripheral persuasion methods, delivered through rational and emotional persuasion strategies, influence cognitive engagement and information processing during visual search tasks.MethodsParticipants were allocated into four groups based on the media type (video vs. text) and the persuasion route (central vs. peripheral). The early and late stages of attentional processing were examined through the N1, P2, and P3 ERP components.ResultsThe results demonstrated a pronounced N1 amplitude in response to text-based peripheral persuasion, indicating enhanced early attentional engagement. Additionally, parallel search tasks revealed a larger P3 amplitude for central versus peripheral routes, suggesting significant cognitive resource allocation during tasks requiring higher attention.DiscussionThese findings underscore the nuanced role of persuasive strategies in modulating attentional resources and cognitive processing. The study offers insights into designing more effective communication messages and highlights the potential for tailored persuasion approaches to influence audience engagement and information processing, with implications for public health campaigns and beyond.","PeriodicalId":12368,"journal":{"name":"Frontiers in Behavioral Neuroscience","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142180017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-06DOI: 10.3389/fnbeh.2024.1458502
Deirdre M. McCarthy, Cynthia Vied, Mia X. Trupiano, Angeli J. Canekeratne, Yuan Wang, Christopher Schatschneider, Pradeep G. Bhide
IntroductionFragile X syndrome is an inherited X-linked disorder associated with intellectual disabilities that begin in childhood and last a lifetime. The symptoms overlap with autism spectrum disorder, and the syndrome predominantly affects males. Consequently, FXS research tends to favor analysis of social behaviors in males, leaving a gap in our understanding of other behavioral traits, especially in females.MethodsWe used a mouse model of FXS to analyze developmental, behavioral, neurochemical, and transcriptomic profiles in males and females.ResultsOur behavioral assays demonstrated locomotor hyperactivity, motor impulsivity, increased “approach” behavior in an approach-avoidance assay, and deficits in nest building behavior. Analysis of brain neurotransmitter content revealed deficits in striatal GABA, glutamate, and serotonin content. RNA sequencing of the ventral striatum unveiled expression changes associated with neurotransmission as well as motivation and substance use pathways. Sex differences were identified in nest building behavior, striatal neurotransmitter content, and ventral striatal gene expression.DiscussionIn summary, our study identified sex differences in specific behavioral, neurotransmitter, and gene expression phenotypes and gene set enrichment analysis identified significant enrichment of pathways associated with motivation and drug reward.
{"title":"Behavioral, neurotransmitter and transcriptomic analyses in male and female Fmr1 KO mice","authors":"Deirdre M. McCarthy, Cynthia Vied, Mia X. Trupiano, Angeli J. Canekeratne, Yuan Wang, Christopher Schatschneider, Pradeep G. Bhide","doi":"10.3389/fnbeh.2024.1458502","DOIUrl":"https://doi.org/10.3389/fnbeh.2024.1458502","url":null,"abstract":"IntroductionFragile X syndrome is an inherited X-linked disorder associated with intellectual disabilities that begin in childhood and last a lifetime. The symptoms overlap with autism spectrum disorder, and the syndrome predominantly affects males. Consequently, FXS research tends to favor analysis of social behaviors in males, leaving a gap in our understanding of other behavioral traits, especially in females.MethodsWe used a mouse model of FXS to analyze developmental, behavioral, neurochemical, and transcriptomic profiles in males and females.ResultsOur behavioral assays demonstrated locomotor hyperactivity, motor impulsivity, increased “approach” behavior in an approach-avoidance assay, and deficits in nest building behavior. Analysis of brain neurotransmitter content revealed deficits in striatal GABA, glutamate, and serotonin content. RNA sequencing of the ventral striatum unveiled expression changes associated with neurotransmission as well as motivation and substance use pathways. Sex differences were identified in nest building behavior, striatal neurotransmitter content, and ventral striatal gene expression.DiscussionIn summary, our study identified sex differences in specific behavioral, neurotransmitter, and gene expression phenotypes and gene set enrichment analysis identified significant enrichment of pathways associated with motivation and drug reward.","PeriodicalId":12368,"journal":{"name":"Frontiers in Behavioral Neuroscience","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142180044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ObjectiveDepression may be accompanied by cognitive impairment, but its pathogenesis remains unclear. This study aims to investigate the protective effects of fluoxetine on behavioral performance and prefrontal cortex neuronal damage in rats with depression-associated cognitive impairment, based on the observation of VGLUT2 protein expression.MethodsForty-five SPF-grade male SD rats were randomly divided into three groups (n = 15): normal control group (CON), depression group (DD), and fluoxetine group (DD + F). The CON group was reared normally, while the DD and DD + F groups underwent chronic unpredictable mild stress (CUMS) combined with social isolation to induce a depression-related cognitive dysfunction model. After modeling, the DD + F group was treated with fluoxetine (10 mg/kg, ig) for 14 days. Behavioral tests were performed to assess changes in mood, cognition, learning, and social abilities. Histopathological observations were made to examine pathological changes, neuronal apoptosis, ultrastructure, and dendritic spine density in the prefrontal cortex. The concentration, relative expression level, and mRNA expression of VGLUT2 protein were also measured. Finally, a correlation analysis was performed between the relative expression level and mRNA expression of VGLUT2 protein and the pathological changes in neurons.ResultsCompared to the CON group, the DD group exhibited decreased body weight, anhedonia, increased behavioral despair, reduced locomotor activity and spontaneous exploratory behavior, impaired spatial learning and memory, and decreased social interaction and social cognitive ability. Pathological damage was observed in the prefrontal cortex, with neuronal apoptosis, ultrastructural damage, and reduced neuroplasticity. The concentration, relative expression, and mRNA expression levels of VGLUT2 protein were decreased. Following fluoxetine intervention, the above behavioral phenotypes improved; pathological damage showed varying degrees of recovery; and the concentration, relative expression, and mRNA expression levels of VGLUT2 protein increased. Finally, there was a significant correlation between VGLUT2 protein expression and pathological changes in the prefrontal cortex.ConclusionAfter 28 days of CUMS combined with isolation rearing, rats exhibited impairments in mood, cognition, learning, and social abilities, with neuronal damage and decreased VGLUT2 protein levels in the prefrontal cortex. Following fluoxetine intervention, VGLUT2 protein expression increased, neuronal repair in the prefrontal cortex occurred, depressive-like behavior improved, and cognitive learning and social abilities were restored.
{"title":"VGLUT2 may improve cognitive function in depressed rats by protecting prefrontal cortex neurons","authors":"Longfei Liu, Yongxue Hu, Qing Shan, Peifan Li, Tianpei Ma, Yiming Wang","doi":"10.3389/fnbeh.2024.1453161","DOIUrl":"https://doi.org/10.3389/fnbeh.2024.1453161","url":null,"abstract":"ObjectiveDepression may be accompanied by cognitive impairment, but its pathogenesis remains unclear. This study aims to investigate the protective effects of fluoxetine on behavioral performance and prefrontal cortex neuronal damage in rats with depression-associated cognitive impairment, based on the observation of VGLUT2 protein expression.MethodsForty-five SPF-grade male SD rats were randomly divided into three groups (<jats:italic>n</jats:italic> = 15): normal control group (CON), depression group (DD), and fluoxetine group (DD + F). The CON group was reared normally, while the DD and DD + F groups underwent chronic unpredictable mild stress (CUMS) combined with social isolation to induce a depression-related cognitive dysfunction model. After modeling, the DD + F group was treated with fluoxetine (10 mg/kg, ig) for 14 days. Behavioral tests were performed to assess changes in mood, cognition, learning, and social abilities. Histopathological observations were made to examine pathological changes, neuronal apoptosis, ultrastructure, and dendritic spine density in the prefrontal cortex. The concentration, relative expression level, and mRNA expression of VGLUT2 protein were also measured. Finally, a correlation analysis was performed between the relative expression level and mRNA expression of VGLUT2 protein and the pathological changes in neurons.ResultsCompared to the CON group, the DD group exhibited decreased body weight, anhedonia, increased behavioral despair, reduced locomotor activity and spontaneous exploratory behavior, impaired spatial learning and memory, and decreased social interaction and social cognitive ability. Pathological damage was observed in the prefrontal cortex, with neuronal apoptosis, ultrastructural damage, and reduced neuroplasticity. The concentration, relative expression, and mRNA expression levels of VGLUT2 protein were decreased. Following fluoxetine intervention, the above behavioral phenotypes improved; pathological damage showed varying degrees of recovery; and the concentration, relative expression, and mRNA expression levels of VGLUT2 protein increased. Finally, there was a significant correlation between VGLUT2 protein expression and pathological changes in the prefrontal cortex.ConclusionAfter 28 days of CUMS combined with isolation rearing, rats exhibited impairments in mood, cognition, learning, and social abilities, with neuronal damage and decreased VGLUT2 protein levels in the prefrontal cortex. Following fluoxetine intervention, VGLUT2 protein expression increased, neuronal repair in the prefrontal cortex occurred, depressive-like behavior improved, and cognitive learning and social abilities were restored.","PeriodicalId":12368,"journal":{"name":"Frontiers in Behavioral Neuroscience","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142180019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-05DOI: 10.3389/fnbeh.2024.1441910
Artem Sinegubov, Vyacheslav Dyachuk
BackgroundMK-801 is a drug widely used in preclinical studies to model schizophrenia in animals. Its distinctive feature is the ability to mimic pathological changes in social interactions. Unlike humans, rodents rely heavily on their sense of smell for social interaction. Since, as previously demonstrated, it also impairs neurogenesis, we set out to determine whether olfactory impairment is associated with chronic administration of the drug.MethodsThe mice were divided into two groups, of which one was administered the drug for 3 weeks, and the other only once. Olfaction and social transfer of food preferences were tested after the drug administration period. At the end of the experiment, an immunofluorescence study was performed to determine differences in neurogenesis in the olfactory bulbs.ResultsAn olfactory deficit was observed in animals that received the drug for 3 weeks. These changes were also accompanied by an abnormal lack of food preference in the social transmission test. As a result of a morphological study, a pronounced decrease in the number of new neurons was found in the olfactory bulbs of the animals that had received the drug.ConclusionOur results indicate that at least some of the impairments in social behavior of the animals exposed to NMDA receptor antagonists are likely caused by changes in the sense of smell. These changes are associated with disruptions of neurogenesis.
{"title":"Chronic exposure to MK-801 leads to olfactory deficits and reduced neurogenesis in the olfactory bulbs of adult male mice","authors":"Artem Sinegubov, Vyacheslav Dyachuk","doi":"10.3389/fnbeh.2024.1441910","DOIUrl":"https://doi.org/10.3389/fnbeh.2024.1441910","url":null,"abstract":"BackgroundMK-801 is a drug widely used in preclinical studies to model schizophrenia in animals. Its distinctive feature is the ability to mimic pathological changes in social interactions. Unlike humans, rodents rely heavily on their sense of smell for social interaction. Since, as previously demonstrated, it also impairs neurogenesis, we set out to determine whether olfactory impairment is associated with chronic administration of the drug.MethodsThe mice were divided into two groups, of which one was administered the drug for 3 weeks, and the other only once. Olfaction and social transfer of food preferences were tested after the drug administration period. At the end of the experiment, an immunofluorescence study was performed to determine differences in neurogenesis in the olfactory bulbs.ResultsAn olfactory deficit was observed in animals that received the drug for 3 weeks. These changes were also accompanied by an abnormal lack of food preference in the social transmission test. As a result of a morphological study, a pronounced decrease in the number of new neurons was found in the olfactory bulbs of the animals that had received the drug.ConclusionOur results indicate that at least some of the impairments in social behavior of the animals exposed to NMDA receptor antagonists are likely caused by changes in the sense of smell. These changes are associated with disruptions of neurogenesis.","PeriodicalId":12368,"journal":{"name":"Frontiers in Behavioral Neuroscience","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142180018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-04DOI: 10.3389/fnbeh.2024.1457894
Mazyar Abdollahi Nejat, Oliver Stiedl, August B. Smit, Ronald E. van Kesteren
Locomotor activity can serve as a readout to identify discomfort and pain. Therefore, monitoring locomotor activity following interventions that induce potential discomfort may serve as a reliable method for evaluating animal health, complementing conventional methods such as body weight measurement. In this study, we used the digital ventilated cage (DVC®) system for the assessment of circadian locomotor activity, in addition to body weight monitoring, following intracranial stereotaxic surgery in an Alzheimer’s disease mouse model (C57BL/6J/APPswe/PSEN1dE9). Stereotaxic surgery did not affect the organization of circadian locomotor activity of both 7–8-week-old and 19–21-week-old mice. However, we observed that both young and old mice exhibited a significant decrease in activity during the dark phase. Also, our study shows that changes in locomotor activity exhibit higher sensitivity in detecting alterations indicative of animal health compared to measuring body weight. In contrast to 7–8-week-old mice, where we observed no genotypic differences in locomotor activity, 19–21-week-old APP/PS1 mice showed increased locomotor activity compared to wild-type mice. Furthermore, our analyses revealed that a subset of the 7–8-week-old mice showed increased locomotor activity during the initial peak of the dark phase. One mouse experienced sudden death early in life, possibly due to epileptic seizures. Altogether, our findings affirm continuous activity measurements as used in the DVC® as a highly valuable objective method for post-surgical welfare monitoring. Its discerning capacity not only facilitates circadian locomotor rhythm assessment but also enables the identification of individual aberrant activity patterns, possibly indicative of epileptic seizures.
{"title":"Continuous locomotor activity monitoring to assess animal welfare following intracranial surgery in mice","authors":"Mazyar Abdollahi Nejat, Oliver Stiedl, August B. Smit, Ronald E. van Kesteren","doi":"10.3389/fnbeh.2024.1457894","DOIUrl":"https://doi.org/10.3389/fnbeh.2024.1457894","url":null,"abstract":"Locomotor activity can serve as a readout to identify discomfort and pain. Therefore, monitoring locomotor activity following interventions that induce potential discomfort may serve as a reliable method for evaluating animal health, complementing conventional methods such as body weight measurement. In this study, we used the digital ventilated cage (DVC<jats:sup>®</jats:sup>) system for the assessment of circadian locomotor activity, in addition to body weight monitoring, following intracranial stereotaxic surgery in an Alzheimer’s disease mouse model (C57BL/6J/APPswe/PSEN1dE9). Stereotaxic surgery did not affect the organization of circadian locomotor activity of both 7–8-week-old and 19–21-week-old mice. However, we observed that both young and old mice exhibited a significant decrease in activity during the dark phase. Also, our study shows that changes in locomotor activity exhibit higher sensitivity in detecting alterations indicative of animal health compared to measuring body weight. In contrast to 7–8-week-old mice, where we observed no genotypic differences in locomotor activity, 19–21-week-old APP/PS1 mice showed increased locomotor activity compared to wild-type mice. Furthermore, our analyses revealed that a subset of the 7–8-week-old mice showed increased locomotor activity during the initial peak of the dark phase. One mouse experienced sudden death early in life, possibly due to epileptic seizures. Altogether, our findings affirm continuous activity measurements as used in the DVC<jats:sup>®</jats:sup> as a highly valuable objective method for post-surgical welfare monitoring. Its discerning capacity not only facilitates circadian locomotor rhythm assessment but also enables the identification of individual aberrant activity patterns, possibly indicative of epileptic seizures.","PeriodicalId":12368,"journal":{"name":"Frontiers in Behavioral Neuroscience","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142180020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BackgroundA rodent autism spectrum disorder (ASD) model based on prenatal exposure to valproic acid (VPA) is widely recognized as a prominent model. Social behavior in rodent ASD models has primarily been evaluated through a three-chamber approach test. However, in this study, we focused on social attention in the VPA model of ASD.MethodsIn male C57BL/6 J mice, attentional behaviors toward conspecifics were examined through reaching tasks around 9–11 weeks of age. On embryonic day 12.5, pregnant mice underwent a subcutaneous injection of 600 mg/kg VPA sodium salt dissolved in 0.9% saline solution (VPA group) or saline solution alone (Sal group) into their neck fat. Thirty-six mice—nine each in the VPA and saline groups, and 18 partners—underwent training in reaching behavior. Subsequently, we examined whether the VPA or Sal group demonstrated focused attention toward their partners during reaching tasks. A two-way analysis of variance (ANOVA) (condition [VPA/Sal] × situation [face-to-face (attention)/not paying attention (not attention)]) was conducted on the average success rate of the situation. Additionally, we measured the duration of sniffing behavior between pairs of mice in an open field twice in total at 4 and 8 weeks of age before reaching task. The pairs were constructed by pairing a VPA or Sal group mouse with its partner, with the objective of facilitating initial encounters between the mice. A one-way ANOVA was conducted on the average duration of sniffing behavior data from 4 weeks and a second one-way ANOVA on data from 8 weeks.ResultsThe analysis revealed a significant interaction between condition and situation in the reaching task [<jats:italic>F</jats:italic> (1, 28) = 6.75, <jats:italic>p</jats:italic> = 0.015, η<jats:sub>p</jats:sub><jats:sup>2</jats:sup> = 0.19]. The simple main effect test exhibited that the “not paying attention” rate was significantly higher than that of the “face-to-face” in the VPA group (<jats:italic>p</jats:italic> < 0.01). The results revealed a not significant difference in the average duration of sniffing behavior at 4 weeks [<jats:italic>F</jats:italic> (3, 32) = 2.71, <jats:italic>p</jats:italic> = 0.06, <jats:italic>n.s.</jats:italic>, η<jats:sub>p</jats:sub><jats:sup>2</jats:sup> = 0.20], but significant difference at 8 weeks [<jats:italic>F</jats:italic> (3, 32) = 4.12, <jats:italic>p</jats:italic> < 0.05, η<jats:sub>p</jats:sub><jats:sup>2</jats:sup> = 0.28]. Multiple comparisons using the Bonferroni method revealed significant differences in the sniffing duration at 8 weeks between from the partner toward the VPA mouse and from the partner toward the Sal mouse (<jats:italic>p</jats:italic> < 0.05).ConclusionThe VPA rodent model of ASD exhibited differences in social attention compared to the saline group. By focusing on social attention and exploring various ASD models, insights can be gained from the neural mechanisms underlying gaze abnormalities during social interact
{"title":"Impairments of social interaction in a valproic acid model in mice","authors":"Masatoshi Ukezono, Yoshiyuki Kasahara, Chihiro Yoshida, Yuki Murakami, Takashi Okada, Yuji Takano","doi":"10.3389/fnbeh.2024.1430267","DOIUrl":"https://doi.org/10.3389/fnbeh.2024.1430267","url":null,"abstract":"BackgroundA rodent autism spectrum disorder (ASD) model based on prenatal exposure to valproic acid (VPA) is widely recognized as a prominent model. Social behavior in rodent ASD models has primarily been evaluated through a three-chamber approach test. However, in this study, we focused on social attention in the VPA model of ASD.MethodsIn male C57BL/6 J mice, attentional behaviors toward conspecifics were examined through reaching tasks around 9–11 weeks of age. On embryonic day 12.5, pregnant mice underwent a subcutaneous injection of 600 mg/kg VPA sodium salt dissolved in 0.9% saline solution (VPA group) or saline solution alone (Sal group) into their neck fat. Thirty-six mice—nine each in the VPA and saline groups, and 18 partners—underwent training in reaching behavior. Subsequently, we examined whether the VPA or Sal group demonstrated focused attention toward their partners during reaching tasks. A two-way analysis of variance (ANOVA) (condition [VPA/Sal] × situation [face-to-face (attention)/not paying attention (not attention)]) was conducted on the average success rate of the situation. Additionally, we measured the duration of sniffing behavior between pairs of mice in an open field twice in total at 4 and 8 weeks of age before reaching task. The pairs were constructed by pairing a VPA or Sal group mouse with its partner, with the objective of facilitating initial encounters between the mice. A one-way ANOVA was conducted on the average duration of sniffing behavior data from 4 weeks and a second one-way ANOVA on data from 8 weeks.ResultsThe analysis revealed a significant interaction between condition and situation in the reaching task [<jats:italic>F</jats:italic> (1, 28) = 6.75, <jats:italic>p</jats:italic> = 0.015, η<jats:sub>p</jats:sub><jats:sup>2</jats:sup> = 0.19]. The simple main effect test exhibited that the “not paying attention” rate was significantly higher than that of the “face-to-face” in the VPA group (<jats:italic>p</jats:italic> &lt; 0.01). The results revealed a not significant difference in the average duration of sniffing behavior at 4 weeks [<jats:italic>F</jats:italic> (3, 32) = 2.71, <jats:italic>p</jats:italic> = 0.06, <jats:italic>n.s.</jats:italic>, η<jats:sub>p</jats:sub><jats:sup>2</jats:sup> = 0.20], but significant difference at 8 weeks [<jats:italic>F</jats:italic> (3, 32) = 4.12, <jats:italic>p</jats:italic> &lt; 0.05, η<jats:sub>p</jats:sub><jats:sup>2</jats:sup> = 0.28]. Multiple comparisons using the Bonferroni method revealed significant differences in the sniffing duration at 8 weeks between from the partner toward the VPA mouse and from the partner toward the Sal mouse (<jats:italic>p</jats:italic> &lt; 0.05).ConclusionThe VPA rodent model of ASD exhibited differences in social attention compared to the saline group. By focusing on social attention and exploring various ASD models, insights can be gained from the neural mechanisms underlying gaze abnormalities during social interact","PeriodicalId":12368,"journal":{"name":"Frontiers in Behavioral Neuroscience","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142180043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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