Biology subjects

Burguiere, E.

Publications and source records attributed to Burguiere, E..

2 recordsLinked to original sources

bioRxiv2019

A cross-species assessment of cognitive flexibility in compulsive disorders

BackgroundCompulsive behaviors, one of the core symptoms of Obsessive-Compulsive Disorder (OCD), are defined as repetitive behaviors performed through rigid rituals. The lack of behavioral flexibility has been as being one of the primary causes of compulsions, but studies exploring this dimension have shown inconsistencies in different tasks performed in human and animal models of compulsive behavior. The aim of this study was so to assess the involvement of behavioral flexibility in compulsion, with a similar approach across different species sharing a common symptom of compulsivity.\n\nMethods40 OCD patients, 40 healthy individually matched control subjects, 26 C57BL/6J Sapap3 KO mice and 26 matched wildtype littermates were included in this study. A similar reversal learning task was designed to assess behavioral flexibility in parallel in these two species.\n\nResultsWhen considered as homogeneous groups, OCD patients and KO mice expressing compulsive behaviors did not significantly differ from their controls regarding behavioral flexibility. When clinical subtypes were considered, only patients exhibiting checking compulsions were impaired with more trials needed to reach the reversal criterion. In KO mice, a similarly impaired subgroup was identified. For both species, this impairment did not result in a greater perseveration after reversal, but in a greater lability in their responses in the reversal condition. Moreover, this impairment did not correlate with the severity of compulsive behaviors.\n\nConclusionsIn our cross-species study, we found no consistent link between compulsive behaviors and a lack of behavioral flexibility. However, we showed in both species that the compulsive group was heterogeneous in term of performance in our reversal learning task. Among the compulsive subjects, we identified a subgroup with impaired performance not due to perseverative and rigid behaviors as commonly hypothesized, but rather to an increase in response lability.

neuroscience↗

bioRxiv2019

Mice carrying a humanized Foxp2 knock-in allele show region-specific shifts of striatal Foxp2 expression levels

Genetic and clinical studies of speech and language disorders are providing starting points to unravel underlying neurobiological mechanisms. The gene encoding the transcription factor FOXP2 has been the first example of a gene involved in the development and evolution of this human-specific trait. A number of autosomal-dominant FOXP2 mutations are associated with developmental speech and language deficits indicating that gene dosage plays an important role in the disorder. Comparative genomics studies suggest that two human-specific amino acid substitutions in FOXP2 might have been positively selected during human evolution. A knock-in mouse model carrying these two amino acid changes in the endogenous mouse Foxp2 gene (Foxp2hum/hum) shows profound changes in striatum-dependent behaviour and neurophysiology, supporting a functional role for these changes. However, how this affects Foxp2 expression patterns in different striatal regions and compartments has not been assessed. Here, we characterized Foxp2 protein expression patterns in adult striatal tissue in Foxp2hum/hum mice. Consistent with prior reports in wildtype mice, we find that striatal neurons in Foxp2hum/hum mice and wildtype littermates express Foxp2 in a range from low to high levels. However, we observe a shift towards more cells with higher Foxp2 expression levels in Foxp2hum/hum mice, significantly depending on the striatal region and the compartment. As potential behavioural readout of these shifts in Foxp2 levels across striatal neurons, we employed a morphine sensitization assay. While we did not detect differences in morphine-induced hyperlocomotion during acute treatment, there was an attenuated hyperlocomotion plateau during sensitization in Foxp2hum/hum mice. Taken together, these results suggest that the humanized Foxp2 allele in a mouse background is associated with a shift in striatal Foxp2 protein expression pattern.

neuroscience↗