Effects of bilateral lesions in thalamic reticular nucleus and orbitofrontal cortex in a T-maze perseverative model produced by 8-OH-DPAT in rats

Andrade, Pablo; Fernández‐Guasti, Alonso; Carrillo-Ruíz, José Damián; Ulloa, Rosa Elena; Ramírez, Ylián; Reyes, Rebeca; Jiménez, Fiacro

doi:10.1016/j.bbr.2009.04.026

Cited by 15 publications

(9 citation statements)

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“…In this respect, the inhibitory feedback mechanism of the TRN on the thalamocortical network becomes a potential candidate for controlling and coordinating the orientation of attention. In accordance with this conception, TRN lesions effectively prevented perseverative behavior in rats, while lesions of the orbitofrontal cortex failed to do so [100]. …”

Section: Hypothesesmentioning

confidence: 87%

A thalamic reticular networking model of consciousness

Min

2010

Theor Biol Med Model

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[Background]It is reasonable to consider the thalamus a primary candidate for the location of consciousness, given that the thalamus has been referred to as the gateway of nearly all sensory inputs to the corresponding cortical areas. Interestingly, in an early stage of brain development, communicative innervations between the dorsal thalamus and telencephalon must pass through the ventral thalamus, the major derivative of which is the thalamic reticular nucleus (TRN). The TRN occupies a striking control position in the brain, sending inhibitory axons back to the thalamus, roughly to the same region where they receive afferents.[Hypotheses]The present study hypothesizes that the TRN plays a pivotal role in dynamic attention by controlling thalamocortical synchronization. The TRN is thus viewed as a functional networking filter to regulate conscious perception, which is possibly embedded in thalamocortical networks. Based on the anatomical structures and connections, modality-specific sectors of the TRN and the thalamus appear to be responsible for modality-specific perceptual representation. Furthermore, the coarsely overlapped topographic maps of the TRN appear to be associated with cross-modal or unitary conscious awareness. Throughout the latticework structure of the TRN, conscious perception could be accomplished and elaborated through accumulating intercommunicative processing across the first-order input signal and the higher-order signals from its functionally associated cortices. As the higher-order relay signals run cumulatively through the relevant thalamocortical loops, conscious awareness becomes more refined and sophisticated.[Conclusions]I propose that the thalamocortical integrative communication across first- and higher-order information circuits and repeated feedback looping may account for our conscious awareness. This TRN-modulation hypothesis for conscious awareness provides a comprehensive rationale regarding previously reported psychological phenomena and neurological symptoms such as blindsight, neglect, the priming effect, the threshold/duration problem, and TRN-impairment resembling coma. This hypothesis can be tested by neurosurgical investigations of thalamocortical loops via the TRN, while simultaneously evaluating the degree to which conscious perception depends on the severity of impairment in a TRN-modulated network.

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Section: Hypothesesmentioning

confidence: 87%

A thalamic reticular networking model of consciousness

Min

2010

Theor Biol Med Model

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“…An alternative approach to predictive validity would be to parallel neuromodulatory treatments in OCD. Both bilateral lesions and bilateral low-frequency stimulation of the thalamic reticular nucleus diminished perseverative response to 8-OH-DPAT; although high-frequency stimulation, which more clearly parallels the response to deep brain stimulation in OCD, had no effect (Andrade et al, 2009, Andrade et al, 2010). More recent work suggests that 8-OH-DPAT may also induce perseverative behavior in other contexts, including returning repeatedly to the same location in an open field arena, which has been described as “compulsive checking” behavior (Alkhatib et al, 2013).…”

Section: Pharmacological Modelsmentioning

confidence: 90%

Rodent models of obsessive compulsive disorder: Evaluating validity to interpret emerging neurobiology

Zike

Hong

et al. 2017

Neuroscience

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Obsessive Compulsive Disorder (OCD) is a common neuropsychiatric disorder with unknown molecular underpinnings. Identification of genetic and non-genetic risk factors has largely been elusive, primarily because of a lack of power. In contrast, neuroimaging has consistently implicated the cortico-striatal-thalamo-cortical (CSTC) circuits in OCD. Pharmacological treatment studies also show specificity, with consistent response of OCD symptoms to chronic treatment with serotonin reuptake inhibitors; although most patients are left with residual impairment. In theory, animal models could provide a bridge from the neuroimaging and pharmacology data to an understanding of pathophysiology at the cellular and molecular level. Several mouse models have been proposed using genetic, immunological, pharmacological, and optogenetic tools. These experimental model systems allow testing of hypotheses about the origins of compulsive behavior. Several models have generated behavior that appears compulsive-like, particularly excessive grooming, and some have demonstrated response to chronic serotonin reuptake inhibitors, establishing both face validity and predictive validity. Construct validity is more difficult to establish in the context of a limited understanding of OCD risk factors. Our current models may help us to dissect the circuits and molecular pathways that can elicit OCD-relevant behavior in rodents. We can hope that this growing understanding, coupled with developing technology, will prepare us when robust OCD risk factors are better understood.

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“…Low‐ but not high‐frequency stimulation of the thalamic nucleus was effective in reducing 8‐OHDPAT‐induced perservation in rats (Andrade et al ., 2009). In the rat, quinpirole‐induced repetitive checking model, high frequency stimulation of the subthalamic nucleus reduced compulsive behaviours transiently, as did stimulation of the nucleus accumbens shell and core (Klavir et al ., 2009; Mundt et al ., 2009; Djodari‐Irani et al ., 2011).…”

Section: Deep Brain Stimulation (Dbs)mentioning

confidence: 99%

Translational approaches to obsessive‐compulsive disorder: from animal models to clinical treatment

Fineberg

Chamberlain

Hollander

et al. 2011

British J Pharmacology

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Obsessive-compulsive disorder (OCD) is characterized by obsessions (intrusive thoughts) and compulsions (repetitive ritualistic behaviours) leading to functional impairment. Accumulating evidence links these conditions with underlying dysregulation of fronto-striatal circuitry and monoamine systems. These abnormalities represent key targets for existing and novel treatment interventions. However, the brain bases of these conditions and treatment mechanisms are still not fully elucidated. Animal models simulating the behavioural and clinical manifestations of the disorder show great potential for augmenting our understanding of the pathophysiology and treatment of OCD. This paper provides an overview of what is known about OCD from several perspectives. We begin by describing the clinical features of OCD and the criteria used to assess the validity of animal models of symptomatology; namely, face validity (phenomenological similarity between inducing conditions and specific symptoms of the human phenomenon), predictive validity (similarity in response to treatment) and construct validity (similarity in underlying physiological or psychological mechanisms). We then survey animal models of OC spectrum conditions within this framework, focusing on (i) ethological models; (ii) genetic and pharmacological models; and (iii) neurobehavioural models. We also discuss their advantages and shortcomings in relation to their capacity to identify potentially efficacious new compounds. It is of interest that there has been rather little evidence of 'false alarms' for therapeutic drug effects in OCD models which actually fail in the clinic. While it is more difficult to model obsessive cognition than compulsive behaviour in experimental animals, it is feasible to infer cognitive inflexibility in certain animal paradigms. Finally, key future neurobiological and treatment research areas are highlighted. LINKED ARTICLESThis article is part of a themed issue on Translational Neuropharmacology. To view the other articles in this issue visit http://dx.doi. org/10.1111/bph.2011.164.issue-4 Abbreviations 5CSRTT, 5-choice serial reaction time test; 5-HT, serotonin; APA, American Psychiatric Association; BOLD, blood oxygen level-dependent; CS, conditioned stimulus; DBS, deep brain stimulation; DSM, Diagnostic and Statistical Manual; ELP, excessive lever presses; (f)MRI, (functional) magnetic resonance imaging; ID-ED, intra-dimensional -extra-dimensional; mCPP, meta-chlorophenylpiperazine; NMDA, N methyl-d aspartic acid; O-C, Obsessive-compulsive; OCD, ObsessiveCompulsive Disorder; OCSDs, Obsessive-Compulsive Spectrum Disorders; OFC, Orbitofrontal Cortex; SR, stimulusresponse; SSRIs, selective serotonin reuptake inhibitors; SSRT, stop-signal reaction time BJP British Journal of Pharmacology DOI:10.1111DOI:10. /j.1476DOI:10. -5381.2011 1044 British Journal of Pharmacology (2011) IntroductionObsessive-compulsive disorder (OCD) is a common neuropsychiatric disorder, affecting roughly 2% of the adult population worldwide (Zohar, 1999), and...

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Effects of bilateral lesions in thalamic reticular nucleus and orbitofrontal cortex in a T-maze perseverative model produced by 8-OH-DPAT in rats

Cited by 15 publications

References 43 publications

A thalamic reticular networking model of consciousness

A thalamic reticular networking model of consciousness

Rodent models of obsessive compulsive disorder: Evaluating validity to interpret emerging neurobiology

Translational approaches to obsessive‐compulsive disorder: from animal models to clinical treatment

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