Using mice to model Obsessive Compulsive Disorder: From genes to circuits

Ahmari, Susanne E.

doi:10.1016/j.neuroscience.2015.11.009

Cited by 58 publications

(53 citation statements)

References 164 publications

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“…The present review considered the use and utility of animal models in research on mechanisms underlying the psychiatric disorder, OCD. This review was not intended to summarize the growing area of research using animal models of OCD, as a number of such first-rate publications already exists (Ahmari, 2015; Ahmari and Dougherty, 2015; Albelda and Joel, 2012a,b; Alonso et al, 2015; Boulougouris et al, 2009; Camilla d’Angelo et al, 2014; Diniz et al, 2012; Eilam and Szechtman, 2005b; Eilam et al, 2012; Grados et al, 2015; Gunaydin and Kreitzer, 2016; Hoffman, 2011; Joel, 2006a; Korff and Harvey, 2006; Man et al, 2004; Ting and Feng, 2011b; Wang et al, 2009; Westenberg et al, 2007). Instead, the current synthesis is unique in that it brings together several independent investigators to highlight a few features of their research where animal models serve as exemplars of fruitful questions and areas of investigation into OCD.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, because the spatiotemporal structure of QNP-induced behavior matched the salient features of OCD checking in the human, it was proposed that the QNP preparation constitutes an animal model of OCD compulsions and compulsive checking in particular (Szechtman et al, 1998a). A comprehensive description of the logic and details of this model has been reviewed (Eilam and Szechtman, 2005b; Szechtman et al, 1999; Szechtman and Eilam, 2005) and evaluated by others (Ahmari, 2015; Ahmari and Dougherty, 2015; Albelda and Joel, 2012ab; Alonso et al, 2015; Camilla d’Angelo et al, 2014; Diniz et al, 2012; Hoffman, 2011; Joel, 2006a; Korff and Harvey, 2006; Man et al, 2004; Pallanti et al, 2014; Westenberg et al, 2007). …”

Section: Insights From Analysis and Synthesis Of Compulsive Checkimentioning

confidence: 99%

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Obsessive-compulsive disorder: Insights from animal models

Szechtman

Ahmari

Beninger

et al. 2017

Neuroscience & Biobehavioral Reviews

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Research with animal models of obsessive-compulsive disorder (OCD) shows the following: (1) Optogenetic studies in mice provide evidence for a plausible cause-effect relation between increased activity in cortico-basal ganglia-thalamo-cortical (CBGTC) circuits and OCD by demonstrating the induction of compulsive behavior with the experimental manipulation of the CBGTC circuit. (2) Parallel use of several animal models is a fruitful paradigm to examine the mechanisms of treatment effects of deep brain stimulation in distinct OCD endophenotypes. (3) Features of spontaneous behavior in deer mice constitute a rich platform to investigate the neurobiology of OCD, social ramifications of a compulsive phenotype, and test novel drugs. (4) Studies in animal models for psychiatric disorders comorbid with OCD suggest comorbidity may involve shared neural circuits controlling expression of compulsive behavior. (5) Analysis of compulsive behavior into its constitutive components provides evidence from an animal model for a motivational perspective on OCD. (6) Methods of behavioral analysis in an animal model translate to dissection of compulsive rituals in OCD patients, leading to diagnostic tests.

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Section: Discussionmentioning

confidence: 99%

Section: Insights From Analysis and Synthesis Of Compulsive Checkimentioning

confidence: 99%

Obsessive-compulsive disorder: Insights from animal models

Szechtman

Ahmari

Beninger

et al. 2017

Neuroscience & Biobehavioral Reviews

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“…; Burguière et al . ; Monteiro and Feng, , ; Ahmari, ), adding to the the list of previously known classic striatum‐related disorders, such as Parkinson's and Huntington's disease (Kreitzer and Malenka, ; Plotkin and Surmeier, ).…”

Section: Introductionmentioning

confidence: 99%

“…Striatum function is crucial for this habit formation and for proper psychomotor behaviour, such as motor control, procedural learning and behavioural switching Hilário and Costa, 2008;Steiner and Tseng, 2010;Parent, 2012). Adult striatum dysfunction results in a loss of action-control (Graybiel, 2008) and its dysfunction has recently been linked to obsessive compulsive disorder and acute stress disorder (Ahmari et al 2013;Burguière et al 2014;Monteiro andFeng, 2015, 2017;Ahmari, 2016), adding to the the list of previously known classic striatum-related disorders, such as Parkinson's and Huntington's disease (Kreitzer and Malenka, 2008;Plotkin and Surmeier, 2015).…”

Section: Introductionmentioning

confidence: 99%

Dichotomous parvalbumin interneuron populations in dorsolateral and dorsomedial striatum

Monteiro

Barak

Zhou

et al. 2018

The Journal of Physiology

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Dorsomedial striatum circuitry is involved in goal-directed actions or movements that become habits upon repetition, as encoded by the dorsolateral striatum. An inability to shift from habits can compromise action-control and prevent behavioural adaptation. Although these regions appear to be clearly behaviourally distinct, little is known about their distinct physiology. Parvalbumin (PV) interneurons are a major source of striatal inhibition and are usually considered as a homogeneous population in the entire dorsal striatum. In the present study, we recorded PV interneurons in dorsal striatum slices from wild-type male mice and suggest the existence of two electrophysiological dichotomous populations. We found that PV interneurons located at the dorsomedial striatum region have increased intrinsic excitability compared to PV interneurons in dorsolateral region. We also found that PV interneurons in the dorsomedial region, but not in the dorsolateral striatum region, receive short-latency excitatory inputs from cingulate cortex. Therefore, the results of the present study demonstrate the importance of considering region specific parvalbumin interneuron populations when studying dorsal striatal function.

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“…There are strong parallels between OCD and other ARB-related conditions, and animal models of OCD proposed based on their phenotypic stereotypy profiles, include genetic models (e.g., hyperdopaminergic mutant deer mice [137,138] and Sapap, Slitrk5 and HoxB8 knockout mice [139]), druginduced and some other models [43,140,141]. Zebrafish models of OCD are gaining value in neuropsychiatric research [142][143][144][145].…”

Section: Modeling Obsessive-compulsive Disorder In Zebrafishmentioning

confidence: 99%

Abnormal repetitive behaviors in zebrafish and their relevance to human brain disorders

Zabegalov

Khatsko

Lakstygal

et al. 2019

Behavioural Brain Research

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Abnormal repetitive behaviors (ARBs) are a prominent symptom of numerous human brain disorders and are commonly seen in rodent models. As rodent studies of ARBs continue to dominate the field, mounting evidence suggests that zebrafish (Danio rerio) also display ARB-like phenotypes and may therefore be a novel model organism for ARB research. In addition to practical research advantages, zebrafish share high genetic and physiological homology to humans and rodents, including multiple ARB-related genes and stereotypic behaviors relevant to ARB. Here, we discuss a wide spectrum of stereotypic repetitive behaviors in zebrafish, data on their genetic and pharmacological modulation, and the overall translational relevance of fish ARBs to modeling human brain disorders. Overall, the zebrafish is rapidly emerging as a new promising model to study ARBs and their underlying mechanisms.

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Using mice to model Obsessive Compulsive Disorder: From genes to circuits

Cited by 58 publications

References 164 publications

Obsessive-compulsive disorder: Insights from animal models

Obsessive-compulsive disorder: Insights from animal models

Dichotomous parvalbumin interneuron populations in dorsolateral and dorsomedial striatum

Abnormal repetitive behaviors in zebrafish and their relevance to human brain disorders

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