The neuropeptide Pth2 modulates social behavior and anxiety in zebrafish

Animal behavior is strongly context-dependent and behavioral performance is often modulated by internal state. In particular, different social contexts can alter anxiety levels and modulate social behavior. The vertebrate-specific neuropeptide parathyroid hormone 2 (pth2) is directly regulated by the presence or absence of conspecifics in zebrafish. As its cognate receptor, the parathyroid hormone 2 receptor (pth2r), is widely expressed across the brain, we tested fish lacking the functional Pth2 peptide in several anxiety-related and social paradigms. Rodents lacking PTH2 display increased anxiety-related behavior. Here we show that the propensity to react to sudden stimuli with an escape response is increased in pth2-/- zebrafish, consistent with elevated anxiety. While overall social preference for conspecifics is maintained in pth2-/- fish until the early juvenile stage, we found that both social preference and shoaling are altered later in development. The data presented suggest that the neuropeptide Pth2 modulates several conserved behavioral features, and may thus enable the animal to react appropriately in different social contexts.

Download Full-text

Cerebellar modulation of the reward circuitry and social behavior

Science ◽

10.1126/science.aav0581 ◽

2019 ◽

Vol 363 (6424) ◽

pp. eaav0581 ◽

Cited By ~ 120

Author(s):

Ilaria Carta ◽

Christopher H. Chen ◽

Amanda L. Schott ◽

Schnaude Dorizan ◽

Kamran Khodakhah

Keyword(s):

Autism Spectrum Disorder ◽

Social Behavior ◽

Mental Disorders ◽

Ventral Tegmental Area ◽

Social Preference ◽

Brain Regions ◽

Autism Spectrum ◽

Reward Circuitry ◽

The Social ◽

The Brain

The cerebellum has been implicated in a number of nonmotor mental disorders such as autism spectrum disorder, schizophrenia, and addiction. However, its contribution to these disorders is not well understood. In mice, we found that the cerebellum sends direct excitatory projections to the ventral tegmental area (VTA), one of the brain regions that processes and encodes reward. Optogenetic activation of the cerebello-VTA projections was rewarding and, in a three-chamber social task, these projections were more active when the animal explored the social chamber. Intriguingly, activity in the cerebello-VTA pathway was required for the mice to show social preference in this task. Our data delineate a major, previously unappreciated role for the cerebellum in controlling the reward circuitry and social behavior.

Download Full-text

Structural and functional brain-wide alterations in A350V Iqsec2 mutant mice displaying autistic-like behavior

Translational Psychiatry ◽

10.1038/s41398-021-01289-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Daniela Lichtman ◽

Eyal Bergmann ◽

Alexandra Kavushansky ◽

Nadav Cohen ◽

Nina S. Levy ◽

...

Keyword(s):

Social Behavior ◽

Functional Connectivity ◽

Mouse Model ◽

Ampa Receptor ◽

Social Preference ◽

Autism Spectrum ◽

Receptor Trafficking ◽

Anterior Cingulate ◽

The Impact ◽

Ampa Receptor Trafficking

AbstractIQSEC2 is an X-linked gene that is associated with autism spectrum disorder (ASD), intellectual disability, and epilepsy. IQSEC2 is a postsynaptic density protein, localized on excitatory synapses as part of the NMDA receptor complex and is suggested to play a role in AMPA receptor trafficking and mediation of long-term depression. Here, we present brain-wide structural volumetric and functional connectivity characterization in a novel mouse model with a missense mutation in the IQ domain of IQSEC2 (A350V). Using high-resolution structural and functional MRI, we show that animals with the A350V mutation display increased whole-brain volume which was further found to be specific to the cerebral cortex and hippocampus. Moreover, using a data-driven approach we identify putative alterations in structure–function relations of the frontal, auditory, and visual networks in A350V mice. Examination of these alterations revealed an increase in functional connectivity between the anterior cingulate cortex and the dorsomedial striatum. We also show that corticostriatal functional connectivity is correlated with individual variability in social behavior only in A350V mice, as assessed using the three-chamber social preference test. Our results at the systems-level bridge the impact of previously reported changes in AMPA receptor trafficking to network-level disruption and impaired social behavior. Further, the A350V mouse model recapitulates similarly reported brain-wide changes in other ASD mouse models, with substantially different cellular-level pathologies that nonetheless result in similar brain-wide alterations, suggesting that novel therapeutic approaches in ASD that result in systems-level rescue will be relevant to IQSEC2 mutations.

Download Full-text

Synergistic Effect of Several Neurotransmitters in PFC-NAc-VTA Neural Circuit for the Anti-Depression Effect of Shuganheweitang in a Chronic Unpredictable Mild Stress Model

Natural Product Communications ◽

10.1177/1934578x211002415 ◽

2021 ◽

Vol 16 (3) ◽

pp. 1934578X2110024

Author(s):

Xin Chen ◽

Yuanchun Ma ◽

Xiongjun Mou ◽

Hao Liu ◽

Hao Ming ◽

...

Keyword(s):

Animal Behavior ◽

Neural Circuit ◽

Concentration Level ◽

Brain Regions ◽

Mild Stress ◽

Depression Effect ◽

Monoamine Neurotransmitters ◽

Reward Circuitry ◽

High Doses ◽

The Brain

Depression, a major worldwide mental disorder, leads to massive disability and can result in death. The PFC-NAc-VTA neuro circuit is related to emotional, neurovegetative, and cognitive functions, which emerge as a circuit-level framework for understanding reward deficits in depression. Neurotransmitters, which are widely distributed in different brain regions, are important detected targets for the evaluation of depression. Shuganheweitang (SGHWT) is a popular prescription in clinical therapy for depression. In order to investigate its possible pharmacodynamics and anti-depressive mechanism, the complex plant material was separated into different fractions. These in low and high doses, along with low and high doses of SGHWT were tested in animal behavior tests. The low and high doses of SGHWT were more effective than the various fractions, which indicate the importance of synergistic function in traditional Chinese medicine. Furthermore, amino acid (GABA, Glu) and monoamine neurotransmitters (DA, 5-HT, NA, 5-HIAA) in the PFC-NAc-VTA neuro circuit were investigated by UPLC-MS/MS. The level trend of DA and 5-HT were consistent in the PFC-NAc-VTA neuro circuit, whereas 5-HIAA was decreased in the PFC, Glu was decreased in the PFC and VTA, and NA and GABA were decreased in the NAc. The results indicate that the pathogenesis of depression is associated with dysfunction of the PFC-NAc-VTA neural circuit, mainly through the neural projection effects of neurotransmitters associated with various brain regions in the neural circuit. PCA and OPLS-DA score plots demonstrated the similarities of individuals within each group and the differences among the groups. In this study, SGHWT could regulate the concentration level of different neurotransmitters in the PFC-NAc-VTA neuro circuit to improve the depression, which benefitted from the recognition of the brain reward circuitry in mood disorders.

Download Full-text

Obeticholic Acid Inhibits Anxiety via Alleviating Gut Microbiota-Mediated Microglia Accumulation in the Brain of High-Fat High-Sugar Diet Mice

Nutrients ◽

10.3390/nu13030940 ◽

2021 ◽

Vol 13 (3) ◽

pp. 940

Author(s):

Li Wu ◽

Yuqiu Han ◽

Zhipeng Zheng ◽

Shuai Zhu ◽

Jun Chen ◽

...

Keyword(s):

Metabolic Disorders ◽

Intestinal Barrier ◽

Behavioral Performance ◽

High Fat ◽

Barrier Dysfunction ◽

Obeticholic Acid ◽

Promising Agent ◽

Serum Biochemical ◽

Lipid Metabolites ◽

The Brain

Anxiety is one of the complications of metabolic disorders (MDs). Obeticholic acid (OCA), the bile acids (BAs) derivative, is a promising agent for improving MDs in association with gut dysbiosis. Yet, its protective effect on MDs-driven anxiety remains unknown. Here, we assessed the serum biochemical parameters and behavioral performance by open field and Morris water maze tests in HFHS diet-induced MDs mice after OCA intervention for nine and 18 weeks. Moreover, antibiotics intervention for microbial depletion was conducted simultaneously. We found that OCA treatment inhibited the initiation and progression of anxiety in HFHS diet-MDs mice via a microbiota–BAs–brain axis: OCA decreased the neuroinflammatory microglia and IL-1β expression in the hippocampus, reversed intestinal barrier dysfunction and serum proinflammatory LPS to a normal level, modified the microbial community, including the known anxiety-related Rikenellaceae and Alistipes, and improved the microbial metabolites especially the increased BAs in feces and circulation. Moreover, the OCA-reversed bile acid taurocholate linked disordered serum lipid metabolites and indole derivatives to anxiety as assessed by network analysis. Additionally, microbial depletion with antibiotics also improved the anxiety, microgliosis and BAs enrichment in the experimental MDs mice. Together, these findings provide microbiota–BAs–brain axis as a novel therapeutic target for MDs-associated neuropsychiatric disorders.

Download Full-text

Minds and brains: angels, humans, and brutes

Journal of Neurosurgery ◽

10.3171/jns.1982.57.3.0309 ◽

1982 ◽

Vol 57 (3) ◽

pp. 309-315

Author(s):

Mortimer J. Adler

Keyword(s):

Nervous System ◽

Animal Behavior ◽

Personal Experience ◽

Human Beings ◽

Content Type ◽

The Past ◽

Wide Range ◽

Conceptual Thought ◽

The Brain ◽

Fine Print

✓ In his 1982 Cushing oration, a distinguished philosopher, author, and discerning critic presents a distillate of his phenomenally wide range of personal experience and his familiarity with the great books and teachers of the present and the past. He explores the differences and relationships between human beings, brute animals, and machines. Knowledge of the brain and nervous system contribute to the explanation of all aspects of animal behavior, intelligence, and mentality, but cannot completely explain human conceptual thought.

Download Full-text

A neural circuit linking two sugar sensors regulates satiety-dependent fructose drive in Drosophila

10.1101/2021.04.08.439043 ◽

2021 ◽

Author(s):

Pierre-Yves Musso ◽

Pierre Junca ◽

Michael D Gordon

Keyword(s):

Feeding Behavior ◽

Synaptic Input ◽

Neural Circuit ◽

Internal State ◽

Calcium Activity ◽

Shaped Body ◽

Body Activity ◽

The Brain

ABSTRACTIngestion of certain sugars leads to activation of fructose sensors within the brain of flies, which then sustain or terminate feeding behavior depending on internal state. Here, we describe a three-part neural circuit that links satiety with fructose sensing. We show that AB-FBl8 neurons of the Fan-shaped body display oscillatory calcium activity when hemolymph glycemia is high, and that these oscillations require synaptic input from SLP-AB neurons projecting from the protocerebrum to the asymmetric body. Suppression of activity in this circuit, either by starvation or genetic silencing, promotes specific drive for fructose ingestion. Moreover, neuropeptidergic signaling by tachykinin bridges fan-shaped body activity and Gr43a-mediated fructose sensing. Together, our results demonstrate how a three-layer neural circuit links the detection of two sugars to impart precise satiety-dependent control over feeding behavior.

Download Full-text

Neuropeptides in modulation of Drosophila behavior: how to get a grip on their pleiotropic actions

10.7287/peerj.preprints.27531 ◽

2019 ◽

Author(s):

Dick R Nässel ◽

Dennis Pauls ◽

Wolf Huetteroth

Keyword(s):

Expression Pattern ◽

Internal State ◽

Neurosecretory Cells ◽

Higher Order ◽

Specific Expression ◽

Specific Expression Pattern ◽

Pleiotropic Functions ◽

Pleiotropic Actions ◽

The Brain ◽

Different Levels

Neuropeptides constitute a large and diverse class of signaling molecules that are produced by many types of neurons, neurosecretory cells, endocrines and other cells. Many neuropeptides display pleiotropic actions either as neuromodulators, co-transmitters or circulating hormones, while some play these roles concurrently. Here, we highlight pleiotropic functions of neuropeptides and different levels of neuropeptide signaling in the brain, from context-dependent orchestrating signaling by higher order neurons, to local executive modulation in specific circuits. Additionally, orchestrating neurons receive peptidergic signals from neurons conveying organismal internal state cues and relay these to executive circuits. We exemplify these levels of signaling with four neuropeptides, SIFamide, short neuropeptide F, allatostatin-A and leucokinin, each with a specific expression pattern and level of complexity in signaling.

Download Full-text

How Intelligence is Understood Today

Artificial Societies ◽

10.18254/s207751800016769-4 ◽

2021 ◽

Vol 16 (3) ◽

pp. 0

Author(s):

Rustam Khasanov

Keyword(s):

Animal Behavior ◽

Learning Algorithms ◽

Cognitive Activity ◽

Reward System ◽

Assessment System ◽

New Developments ◽

Intellectual Abilities ◽

Complex Adaptive ◽

The Brain ◽

Adaptive Abilities

The article is devoted to understanding the ways of explaining intellectual abilities in the light of new developments in the field of artificial intelligence and discoveries related to the study of complex adaptive animal behavior based on the reward system. The paper reviews the latest advances in the development of biologically plausible learning algorithms, the purpose of which is to explain the large amount of accumulated data from the field of neuroscience. Within the framework of this approach, reinforcement learning algorithms are proposed as the basis for any kind of cognitive activity. Understanding intelligence as a set of flexible adaptive abilities to achieve a goal provides a new conceptual framework for explaining how the brain works at a functional level. The formation of forecasts for the future, the construction of time steps and the existence of an internal assessment system in such systems is psychologically and biologically plausible and can potentially become a new milestone in the study of intelligence.

Download Full-text

Sickness and the social brain: How the immune system regulates behavior across species

Brain Behavior and Evolution ◽

10.1159/000521476 ◽

2021 ◽

Author(s):

Benjamin A. Devlin ◽

Caroline J. Smith ◽

Staci D. Bilbo

Keyword(s):

Immune System ◽

Social Behavior ◽

Brain Regions ◽

Behavior Changes ◽

Social Brain ◽

Evolutionary Origins ◽

Immune Mediators ◽

The Social ◽

Sickness Behaviors ◽

The Brain

Many instances of sickness critically involve the immune system. The immune system talks to the brain in a bi-directional loop. This discourse affords the immune system immense control, such that it can influence behavior and optimize recovery from illness. These behavioral responses to infection are called sickness behaviors and can manifest in many ways, including changes in mood, motivation, or energy. Fascinatingly, most of these changes are conserved across species, and most organisms demonstrate some form of sickness behaviors. One of the most interesting sickness behaviors, and not immediately obvious, is altered sociability. Here, we discuss how the immune system impacts social behavior, by examining the brain regions and immune mediators involved in this process. We first outline how social behavior changes in response to infection in various species. Next, we explore which brain regions control social behavior and their evolutionary origins. Finally, we describe which immune mediators establish the link between illness and social behavior, in the context of both normal development and infection. Overall, we hope to make clear the striking similarities between the mechanisms that facilitate changes in sociability in derived and ancestral vertebrate, as well as invertebrate, species.

Download Full-text

The Cross-Modal Effects of Sensory Deprivation on Spatial and Temporal Processes in Vision and Audition: A Systematic Review on Behavioral and Neuroimaging Research since 2000

Neural Plasticity ◽

10.1155/2019/9603469 ◽

2019 ◽

Vol 2019 ◽

pp. 1-21 ◽

Cited By ~ 7

Author(s):

Laura Bell ◽

Lisa Wagels ◽

Christiane Neuschaefer-Rube ◽

Janina Fels ◽

Raquel E. Gur ◽

...

Keyword(s):

Systematic Review ◽

Temporal Processing ◽

Neural Plasticity ◽

Sensory Deprivation ◽

Brain Regions ◽

Behavioral Performance ◽

Brain Organization ◽

Processing Resources ◽

The Cross ◽

The Brain

One of the most significant effects of neural plasticity manifests in the case of sensory deprivation when cortical areas that were originally specialized for the functions of the deprived sense take over the processing of another modality. Vision and audition represent two important senses needed to navigate through space and time. Therefore, the current systematic review discusses the cross-modal behavioral and neural consequences of deafness and blindness by focusing on spatial and temporal processing abilities, respectively. In addition, movement processing is evaluated as compiling both spatial and temporal information. We examine whether the sense that is not primarily affected changes in its own properties or in the properties of the deprived modality (i.e., temporal processing as the main specialization of audition and spatial processing as the main specialization of vision). References to the metamodal organization, supramodal functioning, and the revised neural recycling theory are made to address global brain organization and plasticity principles. Generally, according to the reviewed studies, behavioral performance is enhanced in those aspects for which both the deprived and the overtaking senses provide adequate processing resources. Furthermore, the behavioral enhancements observed in the overtaking sense (i.e., vision in the case of deafness and audition in the case of blindness) are clearly limited by the processing resources of the overtaking modality. Thus, the brain regions that were previously recruited during the behavioral performance of the deprived sense now support a similar behavioral performance for the overtaking sense. This finding suggests a more input-unspecific and processing principle-based organization of the brain. Finally, we highlight the importance of controlling for and stating factors that might impact neural plasticity and the need for further research into visual temporal processing in deaf subjects.

Download Full-text