Closed-loop recruitment of striatal interneurons prevents compulsive-like grooming behaviors.

Compulsive behaviors have been associated with striatal hyperactivity. Parvalbumin-positive striatal interneurons (PVIs) in the striatum play a crucial role in regulating striatal activity and suppressing prepotent inappropriate actions. To investigate the potential role of striatal PVIs in regulating compulsive behaviors, we assessed excessive self-grooming-a behavioral metric of compulsive-like behavior-in male Sapap3 knockout mice (Sapap3-KO).

Improvement in OCD symptoms associated with serotoninergic psychedelics: a retrospective online survey.

A renewed interest in the use of psychedelics for treating obsessive compulsive disorder (OCD) has emerged in the last 20 years. But pre-clinical and clinical evidence remain scarce, and little is known about the factor determining the magnitude and persistence of the therapeutic effect. We therefore designed a retrospective online survey to explore, in the general population using psychoactive drugs, their impact on OCD symptoms.

The Sapap3 mouse reconsidered as a comorbid model expressing a spectrum of pathological repetitive behaviours.

Symptom comorbidity is present amongst neuropsychiatric disorders with repetitive behaviours, complicating clinical diagnosis and impeding appropriate treatments. This is of particular importance for obsessive-compulsive disorder (OCD) and Tourette syndrome. Here, we meticulously analysed the behaviour of Sapap3 knockout mice, the recent rodent model predominantly used to study compulsive-like behaviours, and found that its behaviour is more complex than originally and persistently described.

Can we tackle climate change by behavioral hacking of the dopaminergic system?

Climate change is an undeniable fact that will certainly affect millions of people in the following decades. Despite this danger threatening our economies, wellbeing and our lives in general, there is a lack of immediate response at both the institutional and individual level. How can it be that the human brain cannot interpret this threat and act against it to avoid the immense negative consequences that may ensue? Here we argue that this paradox could be explained by the fact that some key brain mechanisms are potentially poorly tuned to take action against a threat that would take full effect only in the long-term.

Of pride and groom: The gains and limits of studying the neuroanatomy of rodent self-grooming in translational research.

In this issue of Neuron, Xie et al. characterize a cell-specific premotor circuit, generating rhythmic orofacial forelimb movements. The authors show that neurons of the caudal part of spinal trigeminal nucleus, expressing Cerebellin-2, are necessary and sufficient for triggering forelimb movements, which form a part of rodent self-grooming.

Reduced Axon Calibre in the Associative Striatum of the Knockout Mouse.

Pathological repetitive behaviours are a common feature of various neuropsychiatric disorders, including compulsions in obsessive-compulsive disorder or tics in Gilles de la Tourette syndrome. Clinical research suggests that compulsive-like symptoms are related to associative cortico-striatal dysfunctions, and tic-like symptoms to sensorimotor cortico-striatal dysfunctions. The knockout mouse (-KO), the current reference model to study such repetitive behaviours, presents both associative as well as sensorimotor cortico-striatal dysfunctions.

CalDAG-GEFI mediates striatal cholinergic modulation of dendritic excitability, synaptic plasticity and psychomotor behaviors.

CalDAG-GEFI (CDGI) is a protein highly enriched in the striatum, particularly in the principal spiny projection neurons (SPNs). CDGI is strongly down-regulated in two hyperkinetic conditions related to striatal dysfunction: Huntington's disease and levodopa-induced dyskinesia in Parkinson's disease. We demonstrate that genetic deletion of CDGI in mice disrupts dendritic, but not somatic, M1 muscarinic receptors (M1Rs) signaling in indirect pathway SPNs.

A cross-species assessment of behavioral flexibility in compulsive disorders.

Lack of behavioral flexibility has been proposed as one underlying cause of compulsions, defined as repetitive behaviors performed through rigid rituals. However, experimental evidence has proven inconsistent across human and animal models of compulsive-like behavior. In the present study, applying a similarly-designed reversal learning task in two different species, which share a common symptom of compulsivity (human OCD patients and Sapap3 KO mice), we found no consistent link between compulsive behaviors and lack of behavioral flexibility.

Bio-inspired benchmark generator for extracellular multi-unit recordings.

The analysis of multi-unit extracellular recordings of brain activity has led to the development of numerous tools, ranging from signal processing algorithms to electronic devices and applications. Currently, the evaluation and optimisation of these tools are hampered by the lack of ground-truth databases of neural signals. These databases must be parameterisable, easy to generate and bio-inspired, i.

Cognitive Dysfunction in Obsessive-Compulsive Disorder.

Obsessive-compulsive disorder (OCD) is a mental disorder featuring obsessions (intrusive thoughts) and compulsions (repetitive behaviors performed in the context of rigid rituals). There is strong evidence for a neurobiological basis of this disorder, involving limbic cortical regions and related basal ganglion areas. However, more research is needed to lift the veil on the precise nature of that involvement and the way it drives the clinical expression of OCD.

Striatal circuits, habits, and implications for obsessive-compulsive disorder.

Increasing evidence implicates abnormalities in corticostriatal circuits in the pathophysiology of obsessive-compulsive disorder (OCD) and OC-spectrum disorders. Parallels between the emergence of repetitive, compulsive behaviors and the acquisition of automated behaviors suggest that the expression of compulsions could in part involve loss of control of such habitual behaviors. The view that striatal circuit dysfunction is involved in OC-spectrum disorders is strengthened by imaging and other evidence in humans, by discovery of genes related to OCD syndromes, and by functional studies in animal models of these disorders.

Humanized Foxp2 accelerates learning by enhancing transitions from declarative to procedural performance.

The acquisition of language and speech is uniquely human, but how genetic changes might have adapted the nervous system to this capacity is not well understood. Two human-specific amino acid substitutions in the transcription factor forkhead box P2 (FOXP2) are outstanding mechanistic candidates, as they could have been positively selected during human evolution and as FOXP2 is the sole gene to date firmly linked to speech and language development. When these two substitutions are introduced into the endogenous Foxp2 gene of mice (Foxp2(hum)), cortico-basal ganglia circuits are specifically affected.

Optogenetic stimulation of lateral orbitofronto-striatal pathway suppresses compulsive behaviors.

Dysfunctions in frontostriatal brain circuits have been implicated in neuropsychiatric disorders, including those characterized by the presence of repetitive behaviors. We developed an optogenetic approach to block repetitive, compulsive behavior in a mouse model in which deletion of the synaptic scaffolding gene, Sapap3, results in excessive grooming. With a delay-conditioning task, we identified in the mutants a selective deficit in behavioral response inhibition and found this to be associated with defective down-regulation of striatal projection neuron activity.

A Navigation Analysis Tool (NAT) to assess spatial behavior in open-field and structured mazes.

Spatial navigation calls upon mnemonic capabilities (e.g. remembering the location of a rewarding site) as well as adaptive motor control (e.

Role of the cerebellar cortex in conditioned goal-directed behavior.

Learning a new goal-directed behavioral task often requires the improvement of at least two processes, including an enhanced stimulus-response association and an optimization of the execution of the motor response. The cerebellum has recently been shown to play a role in acquiring goal-directed behavior, but it is unclear to what extent it contributes to a change in the stimulus-response association and/or the optimization of the execution of the motor response. We therefore designed the stimulus-dependent water Y-maze conditioning task, which allows discrimination between both processes, and we subsequently subjected Purkinje cell-specific mutant mice to this new task.

Spatial navigation impairment in mice lacking cerebellar LTD: a motor adaptation deficit?

L7-PKCI transgenic mice, which lack parallel fiber-Purkinje cell long-term depression (LTD), were tested with two different mazes to dissociate the relative importance of declarative and procedural components of spatial navigation. We show that L7-PKCI mice are deficient in acquisition of an adapted goal-oriented behavior, part of the procedural component of the task. This supports the hypothesis that cerebellar LTD may subserve a general sensorimotor adaptation process shared by motor and spatial learning functions.

Is the cerebellum ready for navigation?

Spatial navigation required the acquisition of at least two complementary processes: the organization of the spatial representation of the environment (declarative learning) and the acquisition of a motor behaviour adapted to the specific context (procedural learning). The potential role of the cerebellum in spatial navigation is part of the debate concerning its role in cognitive function. Experiments ranging from cerebellar patients to animal models have indicated that cerebellar damage affects the processing of spatial information.

Rat anterodorsal thalamic head direction neurons depend upon dynamic visual signals to select anchoring landmark cues.

Head direction cells, which are functionally coupled to 'place' cells of the hippocampus, a structure critically involved in spatial cognition, are likely neural substrates for the sense of direction. Here we studied the mechanism by which head direction cells are principally anchored to background visual cues [M.B.