The estrous cycle modulates early-life adversity effects on mouse avoidance behavior through progesterone signaling DOI Creative Commons
Blake J. Laham, Sahana Murthy, Monica Hanani

et al.

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Dec. 7, 2022

Early-life adversity (ELA) increases the likelihood of neuropsychiatric diagnoses, which are more prevalent in women than men. Since changes reproductive hormone levels can also increase probability anxiety disorders women, we examined effects ELA on adult female mice across estrous cycle. We found that during diestrus, when progesterone relatively high, exhibit increased avoidance behavior and theta oscillation power ventral hippocampus (vHIP). diestrus had higher lower allopregnanolone, a neurosteroid metabolite progesterone, vHIP compared with control-reared mice. Progesterone receptor antagonism normalized mice, while treatment negative allosteric modulator allopregnanolone promoted control These results suggest altered signaling

Language: Английский

External globus pallidus input to the dorsal striatum regulates habitual seeking behavior in male mice DOI Creative Commons
Matthew Baker, Seungwoo Kang, Sa‐Ik Hong

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: July 12, 2023

Abstract The external globus pallidus (GPe) coordinates action-selection through GABAergic projections throughout the basal ganglia. GPe arkypallidal (arky) neurons project exclusively to dorsal striatum, which regulates goal-directed and habitual seeking. However, role of arky in reward-seeking remains unknown. Here, we identified that a majority target dorsolateral striatum (DLS). Using fiber photometry, found activities were higher during random interval (RI; habit) compared ratio (RR; goal) operant conditioning. Support vector machine analysis demonstrated neuron have sufficient information distinguish between RR RI behavior. Genetic ablation this GPe→DLS circuit facilitated shift from Conversely, chemogenetic activation globally reduced seeking behaviors, was blocked by systemic D1R agonism. Our findings reveal constraining male mice, is relevant addictive behaviors other compulsive disorders.

Language: Английский

Citations

20
A brain-to-spinal sensorimotor loop for repetitive self-grooming DOI Creative Commons
Zhiyong Xie, Dapeng Li, Xinyu Cheng

et al.

Neuron, Journal Year: 2021, Volume and Issue: 110(5), P. 874 - 890.e7

Published: Dec. 20, 2021

Language: Английский

Citations

35
Midbrain dopamine neurons arbiter OCD-like behavior DOI Creative Commons
Jinwen Xue, Dandan Qian, Bing-Qian Zhang

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2022, Volume and Issue: 119(46)

Published: Nov. 7, 2022

The neurobiological understanding of obsessive–compulsive disorder (OCD) includes dysregulated frontostriatal circuitry and altered monoamine transmission. Repetitive stereotyped behavior (e.g., grooming), a featured symptom in OCD, has been proposed to be associated with perturbed dopamine (DA) signaling. However, the precise brain circuits participating DA’s control over this behavioral phenotype remain elusive. Here, we identified that DA neurons substantia nigra pars compacta (SNc) orchestrate ventromedial striatum (VMS) microcircuits as well lateral orbitofrontal cortex (lOFC) during self-grooming behavior. SNc–VMS SNc–lOFC dopaminergic projections modulate grooming behaviors striatal microcircuit function differentially. Specifically, activity pathway promotes via D1 receptors, whereas suppresses D2 receptors. SNc neuron thus controls OCD-like both cortical dual gating. These results support pharmacological brain-stimulation treatments for OCD.

Language: Английский

Citations

24
Anxiety-like behavior and microglial activation in the amygdala after acute neuroinflammation induced by microbial neuraminidase DOI Creative Commons
Ana León‐Rodríguez, María del Mar Fernández‐Arjona, Jesús M. Grondona

et al.

Scientific Reports, Journal Year: 2022, Volume and Issue: 12(1)

Published: July 8, 2022

Abstract Short-term behavioral alterations are associated with infection and aid the recovery from sickness. However, concerns have raised that sustained disturbances after acute neuroinflammation could relate to neurological diseases in long run. We aimed explore medium- long-term rats, using a model based on intracerebroventricular administration of enzyme neuraminidase (NA), which is part some pathogenic bacteria viruses. Neurological assessments were performed 2 10 weeks injection NA, was evaluated by gene expression histology. No observed regarding basic functions or locomotor capacity NA-injected rats. they showed reduction unsupported rearing, increased grooming freezing behaviors, indicate anxiety-like behavior. A principal component analysis including larger set parameters further supported such The anxiety profile NA-injection, but not weeks. Concomitantly, amygdala presented number microglial cells showing morphologic bias towards an activated state. similar subtler tendency hypothalamic microglia located paraventricular nucleus. Also, hypothalamus pattern recognition receptor toll-like 4 (TLR4) slightly overexpressed NA injection. These results demonstrate NA-induced provokes behavior medium term, disappears time. Concurrent microgliosis explain Further experiments should aim subtle long-lasting injection, both hypothalamus, as well mild changes.

Language: Английский

Citations

23
A neuronal coping mechanism linking stress-induced anxiety to motivation for reward DOI Creative Commons
Paul M. Klenowski,

Rubing Zhao-Shea,

Timothy G. Freels

et al.

Science Advances, Journal Year: 2023, Volume and Issue: 9(49)

Published: Dec. 6, 2023

Stress coping involves innate and active motivational behaviors that reduce anxiety under stressful situations. However, the neuronal bases directly linking stress, anxiety, motivation are largely unknown. Here, we show acute stressors activate mouse GABAergic neurons in interpeduncular nucleus (IPN). Stress-coping behavior including self-grooming reward sucrose consumption inherently reduced IPN neuron activity. Optogenetic silencing of activation during stress episodes mimicked strategies alleviated anxiety-like behavior. In a model stress-enhanced for seeking, photoinhibition stress-induced sucrose, whereas photoactivation or excitatory inputs from medial habenula potentiated seeking. Single-cell sequencing, fiber photometry, optogenetic experiments revealed stress-activated drive motivated seeking express somatostatin. Together, these data suggest induces motivates to oppose as an anxiolytic stress-coping mechanism.

Language: Английский

Citations

15
A comparison of machine learning methods for quantifying self-grooming behavior in mice DOI Creative Commons

Kassi Correia,

Raegan Walker,

Christopher Pittenger

et al.

Frontiers in Behavioral Neuroscience, Journal Year: 2024, Volume and Issue: 18

Published: Jan. 29, 2024

Background As machine learning technology continues to advance and the need for standardized behavioral quantification grows, commercial open-source automated analysis tools are gaining prominence in neuroscience. We present a comparative of three pipelines—DeepLabCut (DLC) Simple Behavioral Analysis (SimBA), HomeCageScan (HCS), manual scoring—in measuring repetitive self-grooming among mice. Methods Grooming behavior mice was recorded at baseline after water spray or restraint treatments. Videos were processed analyzed parallel using 3 methods (DLC/SimBA, HCS, scoring), quantifying both total number grooming bouts duration. Results Both treatment conditions (water restraint) resulted significant elevation duration bouts. HCS measures significantly elevated relative those derived from scoring: specifically, tended overestimate low levels grooming. DLC/SimBA measurements not different than scoring. However, SimBA scoring; magnitude direction difference depended on condition. Conclusion provides high-throughput pipeline that correlates well with bout data did reliably estimate obtained via

Language: Английский

Citations

6
Ketamine’s rapid and sustained antidepressant effects are driven by distinct mechanisms DOI Creative Commons
Radhika Rawat, Elif Tunc‐Ozcan,

Sara Dunlop

et al.

Cellular and Molecular Life Sciences, Journal Year: 2024, Volume and Issue: 81(1)

Published: Feb. 27, 2024

Abstract Administration of multiple subanesthetic doses ketamine increases the duration antidepressant effects relative to a single dose, but mechanisms mediating this sustained effect are unclear. Here, we demonstrate that ketamine’s rapid and on affective behavior mediated by separate temporally distinct mechanisms. The dose result from increased activity immature neurons in hippocampal dentate gyrus without an increase neurogenesis. Treatment with six over two weeks doubled behavioral after final injection. However, unlike effects, more did not correlate neuron instead correlated numbers calretinin-positive doublecortin-positive neurons. This neurogenesis was associated decrease bone morphogenetic protein (BMP) signaling, known inhibitor Injection BMP4-expressing lentivirus into maintained BMP signaling niche blocked – ketamine, indicating decreased is necessary for effects. Thus, although requiring neurogenesis, require along activity. Understanding dual action should help development new rapid-acting therapies also have safe, reliable,

Language: Английский

Citations

6
Dissection of the relationship between anxiety and stereotyped self-grooming using the Shank3B mutant autistic model, acute stress model and chronic pain model DOI Creative Commons
Haiying Liu, Xin Huang,

Jinwei Xu

et al.

Neurobiology of Stress, Journal Year: 2021, Volume and Issue: 15, P. 100417 - 100417

Published: Nov. 1, 2021

Self-grooming is an innate, cephalo-caudal progression of body cleaning behaviors that are found in normal rodents but exhibit repetitive and stereotyped patterns several mouse models, such as autism spectrum disorders (ASDs). It also recognized a marker stress anxiety. Mice with Shank3B gene knockout (KO) typical ASD-like behavioral abnormalities, including self-grooming increased levels However, the exact relationship between anxiety certain types animal models not clear. We selected three high to compare their parameters. First, we confirmed KO mice (ASD model), acute restraint model (stress chronic inflammatory pain (pain model) all showed open field test (OFT) elevated plus maze (EPM). only ASD produced total grooming duration. The exhibited increasing trend mean used analysis algorithm examine microstructure assess behavior. results distinct microstructures these models. anxiolytic drug diazepam relieved level time was restored partially model, which suggested aggravated duration model. Our indicated behavior may be shared by separate, interacting, neural circuits disease useful understand mechanisms develop potential treatments for

Language: Английский

Citations

32
A neural circuit for excessive feeding driven by environmental context in mice DOI
Hasan Mohammad, Esra Senol, Martin Graf

et al.

Nature Neuroscience, Journal Year: 2021, Volume and Issue: 24(8), P. 1132 - 1141

Published: June 24, 2021

Language: Английский

Citations

30
Parallel ventral hippocampus-lateral septum pathways differentially regulate approach-avoidance conflict DOI Creative Commons

Dylan C.M. Yeates,

Dallas Leavitt, Sajeevan Sujanthan

et al.

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: June 10, 2022

Abstract The ability to resolve an approach-avoidance conflict is critical adaptive behavior. ventral CA3 (vCA3) and CA1 (vCA1) subfields of the hippocampus (vHPC) have been shown facilitate avoidance approach behavior, respectively, in face motivational conflict, but neural circuits by which this subfield-specific regulation implemented unknown. We demonstrate that two distinct pathways from these lateral septum (LS) contribute divergent control. In Long-Evans rats, chemogenetic inhibition vCA3- LS caudodorsal (cd) pathway potentiated towards a learned conflict-eliciting stimulus, while vCA1-LS rostroventral (rv) non-specifically. Additionally, vCA3-LScd inhibited animals were less hesitant explore food during environmental uncertainty, vCA1- LSrv took longer initiate exploration. These findings suggest vHPC influences multiple behavioral systems via differential projections LS, turn send inhibitory centres brain.

Language: Английский

Citations

21