Duplex optogenetic stimulation system modulates compulsive behaviors bidirectionally

Decisions enable us to consider our actions while adjusting behaviors to a relentlessly changing environment. Since conscious decision making requires our full attention and is therefore expensive, we use a cheaper system for everyday and repetitive tasks that run automatically without conscious evaluations, commonly described as habits. The combination of these two systems is highly adaptive. However, if there is a disruption in these systems’ balance, mental illnesses such as Obsessive-Compulsive Disorders (OCD) or addiction may arise. Now, how does a newly acquired memory or behavior transition to a habit? We know that the striatum’s dorsolateral region (DLS) plays a significant role in sustaining successful behaviors and habits manifestation. Furthermore, it has been shown that the micro-circuitry of the DLS is organized into two functional opposing pathways that consist of the direct pathway striatal spiny projection neurons (dSPNs), which facilitate movement, and the indirect pathway SPNs, which inhibit actions. Already Freud wrote in the letters to his friend Fliess that memory and motive are inseparable, and its recollection would have no force or meaning unless it would be coupled to a motive or emotion. Therefore, we hypothesize that emotional-associated cues would directly prime the DLS through the amygdala to turn newly acquired behaviors into habits. We are adding new supporting insight for this hypothesis by using a duplex optogenetic stimulation system of the amygdala input in the DLS, modulating specific compulsive behaviors bidirectionally. These behavior modulations were accompanied by spine density modulations and intrinsic excitability changes in the SPNs of the DLS. Keywords: Compulsions; Habits; Optogenetics; Neuromodulation; Dorsolateral striatum; Amygdala.

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Translational approach to study flexibility as an endophenotype of obsessive compulsive disorders

European Psychiatry ◽

10.1016/j.eurpsy.2014.09.331 ◽

2014 ◽

Vol 29 (S3) ◽

pp. 546-546

Author(s):

N. Benzina ◽

S.L. Mondragon ◽

N. Ouarti ◽

L. Mallet ◽

E. Burguiere

Keyword(s):

Reversal Learning ◽

Behavioral Flexibility ◽

Repetitive Behaviors ◽

Reward Contingency ◽

Neural Basis ◽

Obsessive Compulsive ◽

Compulsive Behaviors ◽

Translational Approach ◽

Obsessive Compulsive Disorders ◽

Compulsive Disorders

Behavioral flexibility is the ability of a subject to change its behavior according to contextual cues. In humans, Obsessive Compulsive Disorders (OCD) is characterized by repetitive behavior, performed through rigid rituals. This phenomenological observation has led to explore the idea that OCD patients may have diminished behavioral flexibility. To address this question we developed innovative translational approaches across multiple species, including human patients suffering from obsessive-compulsive disorders, and rodent genetic models of OCD to provide original data in the perspective of enlightening the neurocognitive bases of compulsive behaviors. Behavioral flexibility may be challenged in experimental tasks such as reversal learning paradigms. In these tasks, the subject has to respond to either of two different visual stimuli but only one stimulus is positively rewarded while the other is not. After this first association has been learned, reward contingency are inverted, so that the previously neutral stimulus is now rewarded, while the previously rewarded stimulus is not. Performance in reversal learning is indexed by the number of perseverative errors committed when participants maintain their response towards previously reinforced stimulus in spite of negative reward. Unsurprisingly, this behavioral task has been adapted to mice using various response modalities (T-maze, lever press, nose-poke). Using animal models of compulsive behaviors give much more possibilities to study the deficient functions and their underlying neural basis that could lead to pathological repetitive behaviors. Here we present new behavioral set-ups that we developed in parallel in human (i.e. healthy subjects and OCD patients) and mice (i.e. controls and SAPAP3-KO mice) to study the role of the behavioral flexibility as a possible endophenotype of OCD. We observed that the subjects suffering of compulsive behaviors showed perseverative maladaptive behaviors in these tasks. By comparing the results of a similar task-design in humans and mouse models we will discuss the pertinence of such translational approach to further study the neurocognitive basis of compulsive behaviors.

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Analogies in behavioral and emotional disorders between dogs and humans

Medycyna Weterynaryjna ◽

10.21521/mw.6151 ◽

2019 ◽

Vol 75 (01) ◽

pp. 6151-2019

Author(s):

MAŁGORZATA GOLEMAN ◽

ANNA OBŁODECKA ◽

WANDA KRUPA ◽

IWONA ROZEMPOLSKA-RUCIŃSKA

Keyword(s):

Emotional Disorders ◽

Behavioral Problems ◽

Affective Disorders ◽

Mental Illnesses ◽

Psychological State ◽

Obsessive Compulsive ◽

The Social ◽

Obsessive Compulsive Disorders ◽

Compulsive Disorders ◽

Neurophysiological Basis

Human-dog interactions not only shape interspecies relationships in the social context, but also affect the emotional and psychological state of both man and animal. One consequence of living in a developed and urbanized environment is an increase in the occurrence of civilization diseases, which include psychological and emotional disorders occurring not only in humans, but also in animals. The aim of the study was to analyze selected behavioral problems of dogs in the context of their equivalents among human mental illnesses. Such similarities have been demonstrated in early-development disorders, affective disorders, personality disorders and obsessive-compulsive disorders. The development of knowledge about emotional disorders manifested by dogs may have significant importance in the prevention and treatment of human mental illnesses by providing information about their genesis, neurophysiological basis and heritability.

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INNOVATIVE DIRECTION IN THEATMENT OF MENTAL ILLNESS USING SYNERGETIC EFFECTS OF BRAIN TISSUES

Science and Education ◽

10.24195/2414-4665-2020-2-8 ◽

2020 ◽

Vol 2020 (2) ◽

pp. 57-64

Author(s):

Konstantin Shevchenko-Bitenskyi ◽

Valeriy Bitenskyi

Keyword(s):

Mental Illness ◽

Nobel Laureate ◽

Modern Medicine ◽

Mental Illnesses ◽

Unknown Etiology ◽

Obsessive Compulsive ◽

Non Linear ◽

Obsessive Compulsive Disorders ◽

Serious Mental Illnesses ◽

Compulsive Disorders

All etiopathogenetic concepts in modern medicine are based on causal, linear and deterministic relationships. The diseases with an unknown etiology obviously do not have pathogenesis and in relation to that there is no adequate therapy to date. Psychopharmacologists create pharma drugs for the treatment of mental illness based on the same linear principles. However, since the 60s of the 20th century, thanks to the discoveries of many great scientists (for example, Ilya Prigozhin –Nobel Laureate), ideas about nonlinear systems in the nature of the Earth and Human began to develop (Haken, 2007). In particular, most of the serious mental illnesses are classified as open, non-linear, unstable, selforganizing systems. It is obviously that these systems should be changed under the influence of “throwing” into their chaotic structure of a disturbing agent, creating new systems instead of painful ones on the basis of adaptive effects of pre- and postconditioning (PreC; PostC). We have examined and carried out a therapy with a “non-linear” complex of effects of cerebral hypo- and hyperthermia, inhalation of xenon (Xe) and nitrous oxide (N₂O) using intravenous induction and inhalation of valproate (normotimic effect) in 85 patients with obsessive-compulsive disorders. A statistically significant (p> 0.001) therapeutic effect has been obtained in almost 100% (92%) of patients.

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Visual event-related potentials in obsessive-compulsive disorders

Electroencephalography and Clinical Neurophysiology ◽

10.1016/s0013-4694(97)89016-9 ◽

1997 ◽

Vol 103 (1) ◽

pp. 211

Author(s):

F Di Russo

Keyword(s):

Event Related Potentials ◽

Obsessive Compulsive ◽

Related Potentials ◽

Obsessive Compulsive Disorders ◽

Compulsive Disorders

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Clinical Obsessive-Compulsive Disorders in Adults and Children

10.1017/cbo9780511973796 ◽

2009 ◽

Cited By ~ 1

Keyword(s):

Obsessive Compulsive ◽

Adults And Children ◽

Obsessive Compulsive Disorders ◽

Compulsive Disorders

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Dysregulation of DNA methylation during development as a potential mechanisms contributing to obsessive compulsive disorders and autism

10.31234/osf.io/udfya ◽

2019 ◽

Author(s):

German I. Todorov ◽

Karthikeyan Mayilvahanan ◽

David Ashurov ◽

Catarina Cunha

Keyword(s):

Mouse Model ◽

Autism Spectrum ◽

Obsessive Compulsive ◽

Cancer Treatments ◽

Knock Out ◽

Treatment Priority ◽

Underlying Mechanisms ◽

Knock Out Mice ◽

Obsessive Compulsive Disorders ◽

Compulsive Disorders

Autism Spectrum Disorder (ASD) is a pervasive developmental disorder, that is raising at a concerning rate. However, underlying mechanisms are still to be discovered. Obsessions and compulsions are the most debilitating aspect of these disorders (OCD), and they are the treatment priority for patients. SAPAP3 knock out mice present a reliable mouse model for repetitive compulsive behavior and are mechanistically closely related to the ASD mouse model Shank3 on a molecular level and AMPA receptor net effect. The phenotype of SAPAP3 knock out mice is obsessive grooming that leads to self-inflicted lesions by 4 months of age. Recent studies have accumulated evidence, that epigenetic mechanisms are important effectors in psychiatric conditions such as ASD and OCD. Methylation is the most studied mechanism, that recently lead to drug developments for more precise cancer treatments. We injected SAPAP3 mice with an epigenetic demethylation drug RG108 during pregnancy and delayed the onset of the phenotype in the offspring by 4 months. This result gives us clues about possible mechanism involved in OCD and ASD. Additionally, it shows that modulation of methylation mechanisms during development might be explored as a preventative treatment in the cases of high inherited risk of certain mental health conditions.

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