Cerebellum-Specific Deletion of the GABAA Receptor δ Subunit Leads to Sex-Specific Disruption of Behavior DOI Creative Commons
Stephanie Rudolph, Chong Guo,

Stan L. Pashkovski

et al.

Cell Reports, Journal Year: 2020, Volume and Issue: 33(5), P. 108338 - 108338

Published: Nov. 1, 2020

Granule cells (GCs) of the cerebellar input layer express high-affinity δ GABAA subunit-containing receptors (δGABAARs) that respond to ambient GABA levels and context-dependent neuromodulators like steroids. We find GC-specific deletion δGABAA (cerebellar [cb] knockout [KO]) decreases tonic inhibition, makes GCs hyperexcitable, in turn, leads differential activation cb output regions as well many cortical subcortical brain areas involved cognition, anxiety-like behaviors, stress response. Cb KO mice display deficits but motor function is normal. Strikingly, alters maternal behavior spontaneous, stress-related, social behaviors specifically females. Our findings establish δGABAARs enable cerebellum control diverse not previously associated with a sex-dependent manner. These insights may contribute better understanding mechanisms underlie behavioral abnormalities psychiatric neurodevelopmental disorders gender bias.

Language: Английский

Neurobiological links between stress and anxiety DOI Creative Commons
Núria Daviu, Michael R. Bruchas, Bita Moghaddam

et al.

Neurobiology of Stress, Journal Year: 2019, Volume and Issue: 11, P. 100191 - 100191

Published: Aug. 13, 2019

Stress and anxiety have intertwined behavioral neural underpinnings. These commonalities are critical for understanding each state, as well their mutual interactions. Grasping the mechanisms underlying this bidirectional relationship will major clinical implications managing a wide range of psychopathologies. After briefly defining key concepts study stress in pre-clinical models, we present circuit, cellular molecular involved either or both anxiety. First, review studies on divergent circuits basolateral amygdala (BLA) emotional valence processing anxiety-like behaviors, how norepinephrine inputs from locus coeruleus (LC) to BLA responsible acute-stress induced We then describe recent revealing new role mitochondrial function within nucleus accumbens (NAc), individual trait rodents, participating link between Next, report findings impact reward encoding through alteration circuit dynamic synchronicity. Finally, work unravelling hypothalamic corticotropin-releasing hormone (CRH) neurons controlling stress-induce behaviors. Altogether, research reviewed here reveals sharing subcortical nodes Understanding overlap these two psychobiological states, might provide alternative strategies manage disorders such post-traumatic disorder (PTSD).

Language: Английский

Citations

374

Animal Models of Depression: What Can They Teach Us about the Human Disease? DOI Creative Commons
Maria Becker, Albert Pinhasov, Asher Ornoy

et al.

Diagnostics, Journal Year: 2021, Volume and Issue: 11(1), P. 123 - 123

Published: Jan. 14, 2021

Depression is apparently the most common psychiatric disease among mood disorders affecting about 10% of adult population. The etiology and pathogenesis depression are still poorly understood. Hence, as for human diseases, animal models can help us understand and, more importantly, may facilitate search therapy. In this review we first describe tests used evaluation depressive-like symptoms in rodents. Then different discuss their strengths weaknesses. These be divided into several categories: genetic models, induced by mental acute chronic stressful situations caused environmental manipulations (i.e., learned helplessness rats/mice), changes brain neuro-transmitters or specific injuries pharmacological tools. spite fact that none completely resembles depression, relevant since they mimic many features observed situation serve a powerful tool study etiology, treatment especially only few patients respond to treatment. Relevance increases also has facets possible etiologies therapies.

Language: Английский

Citations

119

Understanding stress: Insights from rodent models DOI Creative Commons
Fatin Atrooz, Karim A. Alkadhi,

Samina Salim

et al.

Current Research in Neurobiology, Journal Year: 2021, Volume and Issue: 2, P. 100013 - 100013

Published: Jan. 1, 2021

Through incorporating both physical and psychological forms of stressors, a variety rodent models have provided important insights into the understanding stress physiology. Rodent also significant information with regards to mechanistic basis pathophysiology stress-related disorders such as anxiety disorders, depressive illnesses, cognitive impairment post-traumatic disorder. Additionally, served valuable tools in area drug screening development for treatment stress-induced conditions. Although do not accurately reproduce biochemical or physiological parameters response cannot fully mimic natural progression human yet, animal research has answers many scientific questions. In this review article, studies utilizing are described terms their design apparatus, specific focus on capabilities generate reliable behavioral read-out. The focusses utility by discussing examples literature that offer physiologically relevant highlights advancing mission inquiry.

Language: Английский

Citations

109

Quantified Coexpression Analysis of Central Amygdala Subpopulations DOI Creative Commons
Kenneth M. McCullough, Filomene G. Morrison, Jakob Hartmann

et al.

eNeuro, Journal Year: 2018, Volume and Issue: 5(1), P. ENEURO.0010 - 18.2018

Published: Jan. 1, 2018

Abstract Molecular identification and characterization of fear controlling circuitries is a promising path towards developing targeted treatments fear-related disorders. Three-color in situ hybridization analysis was used to determine whether somatostatin (SOM, Sst ), neurotensin (NTS, Nts corticotropin-releasing factor (CRF, Crf tachykinin 2 (TAC2, Tac2 protein kinase c-δ (PKC-δ, Prkcd dopamine receptor (DRD2, Drd2 ) mRNA colocalize male mouse amygdala neurons. Expression colocalization examined across capsular (CeC), lateral (CeL), medial (CeM) compartments the central amygdala. The greatest expression were found CeC CeL. expressed primarily CeL, while -, -expressing neurons distributed between CeL CeM. High levels identified , within little detected any mRNAs These findings provide more detailed understanding molecular mechanisms that regulate development maintenance anxiety behaviors.

Language: Английский

Citations

130

Long-Term Behavioral Effects of Post-weaning Social Isolation in Males and Females DOI Creative Commons
Deena M. Walker, Ashley M. Cunningham,

Jill Gregory

et al.

Frontiers in Behavioral Neuroscience, Journal Year: 2019, Volume and Issue: 13

Published: April 11, 2019

Adolescence is a developmental period associated with vast neural and behavioral changes which are accompanied by altered sensitivity to stimuli, both stressful rewarding. Perturbations, especially during this have been shown alter behavior in adulthood. Social isolation rearing one such perturbation. This review highlights the long-term consequences of adolescent social rodents specific focus on anxiety- addiction-related behaviors. Sex-specific effects discussed where data available. We then consider monoaminergic neurotransmission as possible mechanism for described. research normative perturbed development crucial understanding treating increased vulnerability psychiatric disorders seen humans life stage.

Language: Английский

Citations

117

The Stage of the Estrus Cycle Is Critical for Interpretation of Female Mouse Social Interaction Behavior DOI Creative Commons
Trishala Chari,

Sophie Griswold,

Nick Andrews

et al.

Frontiers in Behavioral Neuroscience, Journal Year: 2020, Volume and Issue: 14

Published: June 30, 2020

Female animals in biomedical research have traditionally been excluded from studies due to the perceived added complexity caused by estrus cycle. However, given importance of sex differences a variety neurological disorders, testing female mice is critical identifying sex-linked effects diseases. In order determine susceptibility simple behaviors hormonal fluctuations cycle, we studied and cycle on behavioral tasks commonly used mouse phenotyping laboratories. Male C57BL/6J were tested small battery short duration tests and, immediately completion each test, females classified using cytology vaginal lavages as sexually-receptive (proestrus estrus) or non-receptive (metestrus diestrus). We showed that there was significant difference 3-chamber social interaction between at different stages their with showing no preferential interest novel compared an empty chamber. Non-receptive same level preference for male did mouse. No within sexes found anxiety (elevated plus maze, holeboard), working memory (novel object recognition) motor learning (repeated rotarod). conclude stage may impact same-sex conspecifics, does not performance elevated holeboard, recognition, rotarod.

Language: Английский

Citations

101

The role of vitamin C in stress-related disorders DOI

Bettina Moritz,

Ariana Ern Schmitz, Ana Lúcia S. Rodrigues

et al.

The Journal of Nutritional Biochemistry, Journal Year: 2020, Volume and Issue: 85, P. 108459 - 108459

Published: July 3, 2020

Language: Английский

Citations

99

Measuring Behavior in the Home Cage: Study Design, Applications, Challenges, and Perspectives DOI Creative Commons
Fabrizio Grieco, Briana J. Bernstein, Barbara Biemans

et al.

Frontiers in Behavioral Neuroscience, Journal Year: 2021, Volume and Issue: 15

Published: Sept. 24, 2021

The reproducibility crisis (or replication crisis) in biomedical research is a particularly existential and under-addressed issue the field of behavioral neuroscience, where, spite efforts to standardize testing assay protocols, several known unknown sources confounding environmental factors add variance. Human interference major contributor variability both within across laboratories, as well novelty-induced anxiety. Attempts reduce human measure more "natural" behaviors subjects has led development automated home-cage monitoring systems. These systems enable prolonged longitudinal recordings, provide large continuous measures spontaneous behavior that can be analyzed multiple time scales. In this review, diverse team neuroscientists product developers share their experiences using such an system combines Noldus PhenoTyper® home-cages video-based tracking software, EthoVision® XT, extract digital biomarkers motor, emotional, social cognitive behavior. After presenting our working definition "home-cage", we compare with conventional out-of-cage tests (e.g., open field) outline various advantages former, including opportunities for within-subject analyses assessments circadian ultradian activity. Next, address technical issues pertaining acquisition data, fine-tuning software potential integration biotelemetry optogenetics. Finally, guidance on which emphasize, how filter, segment, analyze behavior, use analysis scripts. We summarize PhenoTyper applications study neuropharmacology animal models neurodegenerative neuropsychiatric illness. Looking forward, examine current challenges impact new developments. Examples include recognition specific behaviors, unambiguous individuals context, animal-centered ways dealing datasets. Together, advocate by embracing standardized platforms like PhenoTyper, are poised directly assess reproducibility, importantly, features rodent under ethologically relevant scenarios.

Language: Английский

Citations

65

Endocannabinoids, cannabinoids and the regulation of anxiety DOI
Gavin N. Petrie, Andrei S. Nastase, Robert J. Aukema

et al.

Neuropharmacology, Journal Year: 2021, Volume and Issue: 195, P. 108626 - 108626

Published: June 8, 2021

Language: Английский

Citations

59

An overview of the currency and usefulness of behavioral tests used from past to present to assess anxiety, social behavior and depression in rats and mice DOI
Burcu Açıkgöz,

Bahar Dalkiran,

Ayfer Dayı

et al.

Behavioural Processes, Journal Year: 2022, Volume and Issue: 200, P. 104670 - 104670

Published: June 3, 2022

Language: Английский

Citations

42