-
BioRxiv : the Preprint Server For... Jul 2023Relatively little is known about how the peripheral nervous system (PNS) contributes to the patterning of behavior, in which its role transcends the simple execution of...
Relatively little is known about how the peripheral nervous system (PNS) contributes to the patterning of behavior, in which its role transcends the simple execution of central motor commands or mediation of reflexes. We sought to draw inferences to this end in the aeolid nudibranch , which generates a rapid, dramatic defense behavior, "bristling." This behavior involves the coordinated movement of cerata, dozens of venomous appendages emerging from the animal's mantle. Our investigations revealed that bristling constitutes a stereotyped but non-reflexive two-stage behavior: an initial adduction of proximate cerata to sting the offending stimulus (Stage 1), followed by a coordinated radial extension of remaining cerata to create a pincushion-like defensive screen around the animal (Stage 2). In decerebrated specimens, Stage 1 bristling was preserved, while Stage 2 bristling was replaced by slower, uncoordinated, and ultimately maladaptive ceratal movements. We conclude from these observations that 1) the PNS and central nervous system (CNS) mediate Stages 1 and 2 of bristling, respectively; 2) the behavior propagates through the body utilizing both peripheral- and central-origin nerve networks that support different signaling kinetics; and 3) the former network inhibits the latter in the body region being stimulated. These findings extend our understanding of the PNS's computational capacity and provide insight into a neuroethological scheme that may generalize across cephalized animals, in which the CNS and PNS both independently and interactively pattern different aspects of non-reflexive behavior.
PubMed: 37577477
DOI: 10.1101/2023.07.29.551068 -
Current Biology : CB Jun 2024Escape behavior is a set of locomotor actions that move an animal away from threat. While these actions can be stereotyped, it is advantageous for survival that they are...
Escape behavior is a set of locomotor actions that move an animal away from threat. While these actions can be stereotyped, it is advantageous for survival that they are flexible. For example, escape probability depends on predation risk and competing motivations, and flight to safety requires continuous adjustments of trajectory and must terminate at the appropriate place and time. This degree of flexibility suggests that modulatory components, like inhibitory networks, act on the neural circuits controlling instinctive escape. In mice, the decision to escape from imminent threats is implemented by a feedforward circuit in the midbrain, where excitatory vesicular glutamate transporter 2-positive (VGluT2) neurons in the dorsal periaqueductal gray (dPAG) compute escape initiation and escape vigor. Here we tested the hypothesis that local GABAergic neurons within the dPAG control escape behavior by setting the excitability of the dPAG escape network. Using in vitro patch-clamp and in vivo neural activity recordings, we found that vesicular GABA transporter-positive (VGAT) dPAG neurons fire action potentials tonically in the absence of synaptic inputs and are a major source of inhibition to VGluT2 dPAG neurons. Activity in VGAT dPAG cells transiently decreases at escape onset and increases during escape, peaking at escape termination. Optogenetically increasing or decreasing VGAT dPAG activity changes the probability of escape when the stimulation is delivered at threat onset and the duration of escape when delivered after escape initiation. We conclude that the activity of tonically firing VGAT dPAG neurons sets a threshold for escape initiation and controls the execution of the flight action.
PubMed: 38936364
DOI: 10.1016/j.cub.2024.05.068 -
Healthcare (Basel, Switzerland) Jan 2024Challenging behavior (CB), the most common example being extreme self-injurious or aggressive/destructive behavior, is often observed as a major behavior issue in...
Challenging behavior (CB), the most common example being extreme self-injurious or aggressive/destructive behavior, is often observed as a major behavior issue in individuals with severe intellectual disabilities. This study investigated how CB changed among residents of a facility for people with disabilities before and after it was restructured from a traditional format single room shared by two to three individuals with approximately 20 residents lived together to a format featuring private areas with two rooms per resident and a unitcare system. Twenty-one residents of Care Home A, which was rebuilt in the new care format, were selected. Care staff completed a questionnaire one month before, one month after, and six months after residents moved to the new facility. Scores were compared among each time point. The results revealed significant reductions in residents' aggressive, stereotyped, and targeted behaviors, such as hitting their own head and fecal smearing. The major features of the restructured facility were a living space consisting of two private rooms per resident and a shift to unit care for the entire ward. These new features enabled residents to reduce destructive stimuli and made it easier to understand what to do in each private room.
PubMed: 38338171
DOI: 10.3390/healthcare12030288 -
Behavioural Brain Research Apr 2024Dopamine (DA) is mainly involved in locomotor activity, reward processes and maternal behaviors. Rats with KO gene for dopamine transporter (DAT), coding for a truncated...
Dopamine (DA) is mainly involved in locomotor activity, reward processes and maternal behaviors. Rats with KO gene for dopamine transporter (DAT), coding for a truncated DAT protein, are in hyperdopaminergic conditions and thus develop stereotyped behaviors and hyperactivity. Our aim was to test the prior transgenerational modulation of wild and truncated alleles as expressed in heterozygous DAT rats: specifically, we addressed the possible sequelae due to genotype and gender of the ancestors, with regard to behavioral differences in F, F, F rats. We studied non-classical DAT heterozygotes (HETs) based on two specular lines, with putative grand-maternal vs. grand-paternal imprinting. MAT females (F; offspring of KO male and WT female) mated with a KO male to generate MIX offspring (F). Specularly, PAT females (F; offspring of KO female and WT male) mated with a KO male to generate PIX offspring (F). Similarly to PAT, we obtained MUX (F; HET offspring of MAT sire and KO dam); we also observed the F (MYX: HET offspring of KO male and MUX female, thus with DAT-KO maternal grandmother like also for PIX). We studied their circadian cycle of locomotor activity and their behavior in the elevated-plus-maze (EPM). Locomotor hyper-activity occurs in F, the opposite occurs in F, with MYX rats appearing undistinguishable from WT ones. Open-arm preference emerged in PIX and MIX rats. Only MAT and MYX rats showed a significant vulnerability for ADHD-like inattentive symptoms (duration of rearing in the EPM; Viggiano et al., 2002). A risk-taking profile is evident in the F phenotype, while inattentiveness from F progeny tends to be transferred to F. We hypothesize that DAT-related phenotypes result from effective inheritance through pedigree of imprints that are dependent on grandparents, suggesting a protective role for gestation within a hyperdopaminergic uterus. For major features, similar odd (F, F) generations appear opposed to even (F) ones; for minor specific features, the phenotype transfer may affect the progenies with a male but not a female DAT-KO ancestor.
Topics: Rats; Male; Female; Animals; Dopamine Plasma Membrane Transport Proteins; Heterozygote; Reproduction; Phenotype; Cognition
PubMed: 38408522
DOI: 10.1016/j.bbr.2024.114921 -
Molecular Psychiatry Jan 2024Autism spectrum disorder (ASD) comprises a large group of neurodevelopmental conditions featuring, over a wide range of severity and combinations, a core set of...
Curation of causal interactions mediated by genes associated with autism accelerates the understanding of gene-phenotype relationships underlying neurodevelopmental disorders.
Autism spectrum disorder (ASD) comprises a large group of neurodevelopmental conditions featuring, over a wide range of severity and combinations, a core set of manifestations (restricted sociality, stereotyped behavior and language impairment) alongside various comorbidities. Common and rare variants in several hundreds of genes and regulatory regions have been implicated in the molecular pathogenesis of ASD along a range of causation evidence strength. Despite significant progress in elucidating the impact of few paradigmatic individual loci, such sheer complexity in the genetic architecture underlying ASD as a whole has hampered the identification of convergent actionable hubs hypothesized to relay between the vastness of risk alleles and the core phenotypes. In turn this has limited the development of strategies that can revert or ameliorate this condition, calling for a systems-level approach to probe the cross-talk of cooperating genes in terms of causal interaction networks in order to make convergences experimentally tractable and reveal their clinical actionability. As a first step in this direction, we have captured from the scientific literature information on the causal links between the genes whose variants have been associated with ASD and the whole human proteome. This information has been annotated in a computer readable format in the SIGNOR database and is made freely available in the resource website. To link this information to cell functions and phenotypes, we have developed graph algorithms that estimate the functional distance of any protein in the SIGNOR causal interactome to phenotypes and pathways. The main novelty of our approach resides in the possibility to explore the mechanistic links connecting the suggested gene-phenotype relations.
Topics: Humans; Phenotype; Autism Spectrum Disorder; Genetic Predisposition to Disease; Neurodevelopmental Disorders; Gene Regulatory Networks; Autistic Disorder; Genetic Association Studies; Proteome
PubMed: 38102483
DOI: 10.1038/s41380-023-02317-3 -
Scientific Reports Mar 2024Stereotypies are one of the diagnostic criteria for autism spectrum disorder (ASD) and are common to both ASD and intellectual disability (ID). Previous studies have...
Stereotypies are one of the diagnostic criteria for autism spectrum disorder (ASD) and are common to both ASD and intellectual disability (ID). Previous studies have been inconclusive, with some showing a positive correlation between stereotypies and cortisol, while others have shown a negative correlation. We hypothesised and investigated the presence of ASD as one of the variables involved in this discrepancy. We tested the following hypotheses on serum cortisol in a total of 84 hospitalised patients with severe ID and ASD with severe ID. Hypothesis (1) Higher levels of stereotypies are associated with higher levels of serum cortisol. Hypothesis (2) The presence of ASD will moderate the association between stereotypies and high serum cortisol levels. The results of the analysis supported hypotheses (1) and (2). We also found that in the population with ID, serum cortisol levels were significantly lower in the ASD group compared to the non-ASD group. The present findings that the association between stereotypies and serum cortisol levels in people with severe ID is moderated by the presence of ASD suggest that the stress response system may function differently in people with ID and ASD than in the general population.
Topics: Humans; Hydrocortisone; Autism Spectrum Disorder; Intellectual Disability; Stereotyped Behavior; Stereotypic Movement Disorder
PubMed: 38531943
DOI: 10.1038/s41598-024-57459-3 -
BioRxiv : the Preprint Server For... Aug 2023Autism Spectrum Disorders (ASD) are characterized by core behavioral symptoms in the domains of sociability, language/communication, and repetitive or stereotyped...
An alpha 5-GABAa receptor positive allosteric modulator attenuates social and cognitive deficits without changing dopamine system hyperactivity in an animal model for autism.
Autism Spectrum Disorders (ASD) are characterized by core behavioral symptoms in the domains of sociability, language/communication, and repetitive or stereotyped behaviors. Deficits in the prefrontal and hippocampal excitatory/inhibitory balance due to a functional loss of GABAergic interneurons are proposed to underlie these symptoms. Increasing the postsynaptic effects of GABA with compounds that selectively modulate GABAergic receptors could be a potential target for treating ASD symptoms. In addition, deficits in GABAergic interneurons have been linked to dopamine (DA) system dysregulation, and, despite conflicting evidence, abnormalities in the DA system activity may underly some ASD symptoms. Here, we investigated whether the positive allosteric modulator of α5-containing GABA receptors (α5-GABA Rs) SH-053-2'F-R-CH3 (10 mg/kg) attenuates behavioral abnormalities in a rat model for autism based on VPA exposure. We also evaluated if animals exposed to VPA present changes in the ventral tegmental area (VTA) DA system activity using in vivo electrophysiology and if SH-053-2'F-R-CH3 could attenuate these changes. VPA exposure caused male and female rats to present increased repetitive behavior (self-grooming) in early adolescence and deficits in social interaction in adulthood. Male, but not female VPA rats, also presented deficits in recognition memory as adults. SH-053-2'F-R-CH3 attenuated the impairments in sociability and cognitive function in male VPA-exposed rats without attenuating the decreased social interaction in females. Male and female adult VPA-exposed rats also showed an increased VTA DA neuron population activity, which was not changed by SH-053-2'F-R-CH3. Despite sex differences, our findings indicate α5-GABA Rs positive allosteric modulators may effectively attenuate some core ASD symptoms.
PubMed: 37662217
DOI: 10.1101/2023.08.24.554679 -
ELife Apr 2024Complex skills like speech and dance are composed of ordered sequences of simpler elements, but the neuronal basis for the syntactic ordering of actions is poorly...
Complex skills like speech and dance are composed of ordered sequences of simpler elements, but the neuronal basis for the syntactic ordering of actions is poorly understood. Birdsong is a learned vocal behavior composed of syntactically ordered syllables, controlled in part by the songbird premotor nucleus HVC (proper name). Here, we test whether one of HVC's recurrent inputs, mMAN (medial magnocellular nucleus of the anterior nidopallium), contributes to sequencing in adult male Bengalese finches (). Bengalese finch song includes several patterns: (1) comprising stereotyped syllable sequences; (2) , where a given syllable can be followed probabilistically by multiple syllables; and (3) , where individual syllables are repeated variable numbers of times. We found that following bilateral lesions of mMAN, acoustic structure of syllables remained largely intact, but sequencing became more variable, as evidenced by 'breaks' in previously stereotyped chunks, increased uncertainty at branch points, and increased variability in repeat numbers. Our results show that mMAN contributes to the variable sequencing of vocal elements in Bengalese finch song and demonstrate the influence of recurrent projections to HVC. Furthermore, they highlight the utility of species with complex syntax in investigating neuronal control of ordered sequences.
Topics: Male; Animals; Songbirds; Speech; Acoustics; Memory; Stereotyped Behavior
PubMed: 38635312
DOI: 10.7554/eLife.93272 -
Science Advances Jan 2024The ability to predict the future based on past experience lies at the core of the brain's ability to adapt behavior. However, the neural mechanisms that participate in...
The ability to predict the future based on past experience lies at the core of the brain's ability to adapt behavior. However, the neural mechanisms that participate in generating and updating predictions are not clearly understood. Further, the evolutionary antecedents and the prevalence of predictive processing among vertebrates are even less explored. Here, we show evidence of predictive processing via the involvement of cerebellar circuits in larval zebrafish. We presented stereotyped optic flow stimuli to larval zebrafish to evoke swims and discovered that lesioning the cerebellum abolished prediction-dependent modulation of swim latency. When expectations of optic flow direction did not match with reality, error signals arrive at Purkinje cells via the olivary climbing fibers, whereas granule cells and Purkinje cells encode signals of expectation. Strong neural representations of expectation correlate with faster swim responses and vice versa. In sum, our results show evidence for predictive processing in nonmammalian vertebrates with the involvement of cerebellum, an evolutionarily conserved brain structure.
Topics: Animals; Zebrafish; Larva; Cerebellum; Purkinje Cells; Neurons
PubMed: 38170763
DOI: 10.1126/sciadv.adi6470 -
Frontiers in Psychiatry 2024Autism Spectrum Disorders (ASD) are a collection of neurodevelopmental diseases characterized by poor social interaction and communication, a limited range of interests,...
Effects of transcutaneous auricular vagus nerve stimulation and exploration of brain network mechanisms in children with high-functioning autism spectrum disorder: study protocol for a randomized controlled trial.
BACKGROUND
Autism Spectrum Disorders (ASD) are a collection of neurodevelopmental diseases characterized by poor social interaction and communication, a limited range of interests, and stereotyped behavior. High-functioning autism (HFA) indicates a subgroup of individuals with autism who possess cognitive and/or language skills that are within the average to above-normal range for their age. Transcutaneous auricular vagus nerve stimulation (taVNS) holds promise in children with HFA. However, few studies have used randomized controlled trials to validate the effectiveness of taVNS. Therefore, in this study, we intend to provide a study protocol to examine the therapeutic effects of taVNS in individuals diagnosed with HFA and to investigate the process of brain network remodeling in individuals with ASD using functional imaging techniques to observe alterations in large-scale neural networks.
METHODS AND DESIGN
We planned to employ a randomized, double-blind experimental design, including 40 children receiving sham stimulation and 40 children receiving real stimulation. We will assess clinical scales and perform functional imaging examinations before and after the stimulation. Additionally, we will include age- and gender-matched healthy children as controls and conduct functional imaging examinations. We plan first to observe the therapeutic effects of taVNS. Furthermore, we will observe the impact of taVNS stimulation on the brain network.
DISCUSSION
taVNS was a low-risk, easy-to-administer, low-cost, and portable option to modulate the vagus system. taVNS may improve the social performance of HFA. Changes in the network properties of the large-scale brain network may be related to the efficacy of taVNS.
CLINICAL TRIAL REGISTRATION
http://www.chictr.org.cn, identifier ChiCTR2300074035.
PubMed: 38374975
DOI: 10.3389/fpsyt.2024.1337101