Frontiers in Behavioral Neuroscience最新文献

Behavioral copying is a key process in group actions, but it is challenging for individuals with autism spectrum disorder (ASD). We investigated behavioral contagion, or instinctual replication of behaviors, in Krushinky-Molodkina (KM) rats (n = 16), a new potential rodent model for ASD, compared to control Wistar rats (n = 15). A randomly chosen healthy Wistar male ("demonstrator rat") was introduced to the homecage of experimental rats ("observers") 10-14 days before the experiments to become a member of the group. For the implementation of the behavioral contagion experiment, we used the IntelliCage system, where rats can live in a group of 5-6 rats and their water visits can be automatically scored. During the experiment, the demonstrator was taken out of IntelliCage for a pre-test water deprivation and then placed back for the behavioral contagion test. As a result, a drinking behavior of the water-deprived demonstrator rat prompted water-seeking and drinking behaviors in the whole group. Unlike the Wistar controls, KM observers showed fewer visits to the drinking bottles, particularly lacking inspection visits (i.e., visits without drinking). The control group, in contrast, exhibited a dynamic, cascade-like visiting of the water corners. The proportion of activated observers in KM rats was significantly lower, as compared to Wistar ones, and they did not mimic other observer rats. KM rats, therefore, displayed an attenuated pattern of behavioral contagion, highlighting social deficits in this strain. This study suggests that measuring group dynamics of behavioral contagion in an automated, non-invasive setup offers valuable insights into social behavior in rodents.

Extensive behavioral research on adults has shown that retrieval practice is highly beneficial for long-term memory retention. However, limited evidence exists on the developmental course of this benefit. Here, we present data from a behavioral study involving 7-14-year-old children who had to encode a total of 60 weakly semantically related cue-target word pairs using either repeated retrieval or repeated study encoding strategies. Results revealed age-related increases in the ability to benefit from testing during encoding from early middle childhood to early adolescence. In contrast, repeated study during encoding did not lead to developmental improvements in long-term memory retention across this age range. Individual differences in vocabulary knowledge, short-term memory and working memory were positively associated with long-term memory retention only for those participants who encoded the information via repeated study. These results indicate that (1) the mechanisms determining the testing effect may not be fully in place by early middle childhood, (2) the ability to benefit from testing improves over the middle childhood years, and (3) these benefits are not associated with individual differences in memory and high-cognitive functioning. One potential interpretation of these findings is that changes in sleep-dependent consolidation processes during middle childhood may be critical for understanding the observed developmental differences in ability to enhance long-term memory via the testing effect.

There is a striking sex bias in the prevalence and severity of autism spectrum disorder (ASD) with 80% of diagnoses occurring in males. Because the molecular etiology of ASD is likely combinatorial, including interactions across multiple genetic and environmental factors, it is difficult to investigate the physiological mechanisms driving sex-specific differences. Loss of function mutations in TSC1 result in dysregulated mTORC1 signaling and underlie a multi-system disorder known as tuberous sclerosis (TSC). Interestingly, more than 50% of individuals diagnosed with TSC are also diagnosed with ASD, making TSC mutations one of the most prevalent monogenic causes of ASD. Mice harboring targeted deletion of Tsc1 selectively in cerebellar Purkinje neurons, referred to here as Tsc1^mut/mut , have multiple ASD-linked behavioral impairments, including deficits in social interactions, motor coordination, and vocalizations. However, these ASD-linked behavioral deficits have only been investigated using male Tsc1^mut/mut animals. Here, we used cohorts of male and female Tsc1^mut/mut animals to determine if behavioral impairments, previously identified in this model, are similar across sex. Specifically, we measured balance and motor coordination and social interaction behaviors in two age groups across sex. We determined balance and motor coordination deficits are similar in male and female Tsc1^mut/mut mice, and that deficits in the firing of Tsc1^mut/mut Purkinje neurons located in the cerebellar vermis are also similar across sex. However, impairments in social approach behavior were found to be significantly more severe in Tsc1^mut/mut males compared to females. These results indicate the selective deletion of Tsc1 in Purkinje neurons differentially impairs cerebellar circuits based on sex.

Molecular and genetic techniques now allow selective tagging and manipulation of the population of neurons, often referred to as "engram cells," that were active during a specific experience. One common approach to labeling these cells is to use the fos-tTA transgenic mouse (TetTag). In addition to tagging cells active during learning, it is common to examine the reactivation of these cells using immediate early gene (IEG) expression as an index of neural activity. There are currently multiple TetTag lines available. The original line, cryopreserved at MMRRC, contains only the fos-tTA transgene, while Jackson Labs provides a version of the mouse that expresses both the fos-tTA and fos-shEGFP genes. In the current experiments, we examined IEG expression in these two mouse lines. Unexpectedly, we found that Jackson fos-tTA/fos-shEGFP mice express increased levels of c-Fos in the hippocampus compared to wild type animals when examined with immunohistochemistry (IHC). The expression of other IEGs, such as Arc and Egr-1, was not elevated in these mice, suggesting that the overexpression of c-Fos is not the result of increased excitability or broad changes in gene expression. qPCR revealed that Jackson fos-tTA/fos-shEGFP mice express mRNA corresponding to a c-Fos-Exon1-GFP fusion molecule, which may bind to C-Fos antibodies during IHC and inflate apparent c-Fos expression. Jackson fos-tTA/fos-shEGFP mice did not differ from their wild-type counterparts in fear expression or memory, indicating no behavioral effect of the presence of a c-Fos-GFP fusion protein. These results identify a major limitation inherent in the use of Jackson fos-tTA/fos-shEGFP mice.

Animacy perception, the ability to discern living from non-living entities, is crucial for survival and social interaction, as it includes recognizing abstract concepts such as movement, purpose, and intentions. This process involves interpreting cues that may suggest the intentions or actions of others. It engages the temporal cortex (TC), particularly the superior temporal sulcus (STS) and the adjacent region of the inferior temporal cortex (ITC), as well as the dorsomedial prefrontal cortex (dmPFC). However, it remains unclear how animacy is dynamically encoded over time in these brain areas and whether its processing is distributed or localized. In this study, we addressed these questions by employing a symbolic categorization task involving animate and inanimate objects using natural movie stimuli. Simultaneously, electrocorticography were conducted in both the TC and dmPFC. Time-frequency analysis revealed region-specific frequency representations throughout the observation of the movies. Spatial searchlight decoding analysis demonstrated that animacy processing is represented in a distributed manner. Regions encoding animacy information were found to be dispersed across the fundus and lip of the STS, as well as in the ITC. Next, we examined whether these dispersed regions form functional networks. Independent component analysis revealed that the spatial distribution of the component with the most significant animacy information corresponded with the dispersed regions identified by the spatial decoding analysis. Furthermore, Granger causality analysis indicated that these regions exhibit frequency-specific directional functional connectivity, with a general trend of causal influence from the ITC to STS across multiple frequency bands. Notably, a prominent feedback flow in the alpha band from the ITC to both the ventral bank and fundus of the STS was identified. These findings suggest a distributed and functionally interconnected neural substrate for animacy processing across the STS and ITC.

Binge eating (BE) is a highly pervasive maladaptive coping strategy in response to severe early life stress such as emotional and social neglect. BE is described as repeated episodes of uncontrolled eating and is tightly linked with comorbid mental health concerns. Despite social stressors occurring at a young age, the onset of BE typically does not occur until adulthood providing an interval for potential therapeutic intervention. Currently, our knowledge of longitudinal noninvasive digital biomarkers predictive of BE needs further development. Monitoring longitudinal impacts of adolescent social isolation stress on naturalistic behaviors in rats will enable the identification of noninvasive digital markers of disease progression to predict adult eating strategies. Recognizing adolescent naturalistic behaviors shaped by social stress informs our understanding of the underlying neurocircuits most effected. This study aimed to monitor and identify longitudinal behavioral shifts to enhance predictive capabilities in a rat model of social isolation stress-induced BE. We placed Paired (n = 12) and Socially Isolated (SI, n = 12) female rats in observational home cages weekly for seven weeks to evaluate the effect of SI on 10 naturalistic behaviors. All 10 naturalistic behaviors were simultaneously detected and tracked using Noldus Ethovision XT automated recognition software. Composite phenotypic z-scores were calculated by standardizing all 10 behaviors. When transitioning into adulthood, all rats underwent conventional emotionality testing and were exposed to a Western-like high fat diet (WD, 43% kcal from fat) to evaluate BE. Longitudinal assessments revealed SI-induced shifts in adolescent phenotypic z-scores and that sniffing, unsupported rearing, jumping, and twitching were the most susceptible to SI. SI increased emotionality compared to the Paired controls. Finally, we identified adolescent twitching as a digital biomarker of adult WD consumption. Our findings suggest that home cage monitoring can detect disrupted naturalistic behaviors associated with maladaptive coping.

Introduction: Carbonated water (CarbW) affects the swallowing function associated with the action of the brainstem. In addition, CarbW ingestion promotes mean blood flow in the middle cerebral artery, which is associated with blood flow to the frontal and temporal lobes. In this milieu, studies regarding the effect of drinking CarbW on brain activity are of significance. In the present study, we compared the changes in cerebral blood flow in the frontal region before and after the ingestion of CarbW or uncarbonated water (SW).

Methods: Near-infrared spectroscopy was used to continuously measure the cerebral blood flow at 22 channels in the frontal region of 13 healthy young adults for 10 min before and after the ingestion of CarbW or SW. We statistically compared the changes in oxyhemoglobin concentration before and after the ingestion of CarbW or SW.

Results: Compared with that before CarbW ingestion, the oxyhemoglobin concentration in the left frontal region increased after CarbW ingestion. In particular, a significant increase (p < 0.05) was observed in the ch21 region. On the contrary, no marked increase or decrease in cerebral blood flow was observed after SW ingestion compared with that before ingestion.

Discussion: The activated part of the frontal region (ch21) corresponds to the vicinity of the orbitofrontal cortex, which is reportedly activated by rewarding stimuli. In addition, as the orbitofrontal cortex is located at the terminal end of the reward pathway of the mesocortical system, CarbW ingestion might have acted on the dopaminergic reward pathway of the mesocortical system.

Safety learning during threat and adversity is critical for behavioral adaptation, resiliency, and survival. Using a novel mouse paradigm involving thermal threat, we recently demonstrated that safety learning is highly susceptible to social isolation stress. Yet, our previous study primarily considered male mice and did not thoroughly scrutinize the relative impacts of stress on potentially distinct defensive mechanisms implemented by males and females during the thermal safety task. The present study assessed these issues while considering a variety of defensive behaviors related to safety-seeking, escape, coping, protection, ambivalence, and risk-taking. After a two-week social isolation stress period, mice were required to explore a box arena that had thermal threat and safety zones (5 vs. 30°C, respectively). Since visuospatial cues clearly differentiated the threat and safety zones, the majority of the no-stress controls (69-75%) in both sexes exhibited optimal memory formation for the safety zone. In contrast, the majority of the stress-exposed mice in both sexes (69-75%) exhibited robust impairment in memory formation for the safety zone. Furthermore, while the control groups exhibited many robust correlations among various defensive behaviors, the stress-exposed mice in both sexes exhibited disorganized behaviors. Thus, stress severely impaired the proper establishment of safety memory and the structure of defensive behavior, effects that primarily occurred in a sex-independent manner.

Introduction: Anxiety is an emotion necessary for human survival. However, persistent and excessive anxiety can be clinically challenging. Increased anxiety affects daily life and requires early detection and intervention. Therefore, a better understanding of the neural basis of mild anxiety is needed. However, previous studies have focused primarily on resting-state functional magnetic resonance imaging (rs-fMRI) in patients with psychiatric disorders presenting with anxiety. Notably, only a few studies have been conducted on healthy participants, and the relationship between anxiety and functional brain connectivity in the healthy range remains unclear. Therefore, in this study, we aimed to clarify the differences in functional brain connectivity at different degrees of anxiety among healthy participants.

Methods: This study included 48 healthy participants with no history of psychiatric disorders. Participants were administered The General Health Questionnaire (GHQ) 60, a psychological test for assessing anxiety, and the Manifest Anxiety Scale (MAS). The participants then underwent rs-fMRI. Based on the results of each psychological test, the participants were classified into normal and anxiety groups, and the functional connectivity between the two groups was compared using a seed-to-voxel analysis.

Results: Comparison of functional brain connectivity between the normal and anxiety groups classified based on the GHQ60 and MAS revealed differences between brain regions comprising the salience network (SN) in both psychological tests. For the GHQ60, the anxiety group showed reduced connectivity between the right supramarginal gyrus and insular cortex compared with the normal group. However, for the MAS, the anxiety group showed reduced connectivity between the right supramarginal and anterior cingulate cortical gyri compared with the normal group.

Conclusion: Functional connectivity within the SN was reduced in the group with higher anxiety when functional brain connectivity at different anxiety levels was examined in healthy participants. This suggests that anxiety is involved in changes in the functional brain connectivity associated with emotional processing and cognitive control.

The Morris Water Maze (MWM) is the most commonly used assay for evaluating learning and memory in laboratory mice. Despite its widespread use, contemporary reviews have highlighted substantial methodological variation in experimental protocols and that the associated testing procedures are acutely (each trial) and chronically (testing across days) stressful; stress impairs attention, memory consolidation and the retrieval of learned information. Moreover, the interpretation of behavior within the MWM is often difficult because of wall hugging, non-spatial swim strategies, floating, and jumping off the escape platform. Together, these issues may compromise the reproducibility, generalizability, and predictability of experimental results, as well as animal welfare. To address these issues, and as an initial proof-of-principle, we first narrowed the spatial dimensions of the MWM by using a T-insert, which constrained and reduced the overall length of time/distance that the animal must swim in order to navigate to the escape platform, thus reducing stress and off-task behavior. Given the robust performance observed across spatial acquisition (learning and memory) as well as during reversal learning (executive function), we further reduced (by 43%) the overall distance and time that the animal must swim in order to find the escape platform in a bespoke standalone Water T-Maze (WTM). We show, across five experiments, procedural refinements to our protocol and demonstrate robust, reliable and reproducible indicators of learning, memory and executive functioning in a task that is also significantly more efficient (3 days of testing within the WTM vs. 11 days of testing within the MWM). Taken together, our WTM apparatus and protocol are a significant improvement over other water-based apparatuses and protocols for evaluating learning, memory, and executive functioning in laboratory mice.