Reduced Axon Calibre in the Associative Striatum of the Sapap3 Knockout Mouse
Open Access
- 14 October 2021
- journal article
- research article
- Published by MDPI AG in Brain Sciences
- Vol. 11 (10), 1353
- https://doi.org/10.3390/brainsci11101353
Abstract
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 Sapap3 knockout mouse (Sapap3-KO), the current reference model to study such repetitive behaviours, presents both associative as well as sensorimotor cortico-striatal dysfunctions. Previous findings point to deficits in both macro-, as well as micro-circuitry, both of which can be affected by neuronal structural changes. However, to date, structural connectivity has not been analysed. Hence, in the present study, we conducted a comprehensive structural characterisation of both associative and sensorimotor striatum as well as major cortical areas connecting onto these regions. Besides a thorough immunofluorescence study on oligodendrocytes, we applied AxonDeepSeg, an open source software, to automatically segment and characterise myelin thickness and axon area. We found that axon calibre, the main contributor to changes in conduction speed, is specifically reduced in the associative striatum of the Sapap3-KO mouse; myelination per se seems unaffected in associative and sensorimotor cortico-striatal circuits.Funding Information
- Agence national de la recherche (ANR-16-INSERM-SINREP, ANR-19-ICM-DOPALOOPS, BBT-ACTIMYEL, L’Oréal-UNESCO Fellowship 2016, 950-230815, 32454, 34824, 5886, 35450, ANR-10-IAIHU-06 and ANR-11-INBS-0011-NeurATRIS)
- Canadian Institutes of Health Research (CIHR FDN-143263)
- Fonds de Recherche du Québec - Santé (28826)
- Natural Sciences and Engineering Research Council of Canada (RGPIN-2019-07244)
- Canada First Research Excellence Fund (IVADO and TransMedTech)
This publication has 86 references indexed in Scilit:
- Tics are caused by alterations in prefrontal areas, thalamus and putamen, while changes in the cingulate gyrus reflect secondary compensatory mechanismsBMC Neuroscience, 2014
- Impaired adult myelination in the prefrontal cortex of socially isolated miceNature Neuroscience, 2012
- Fiji: an open-source platform for biological-image analysisNature Methods, 2012
- Absence of CNTNAP2 Leads to Epilepsy, Neuronal Migration Abnormalities, and Core Autism-Related DeficitsCell, 2011
- Repetitive Behaviours in Patients with Gilles de la Tourette Syndrome: Tics, Compulsions, or Both?PLOS ONE, 2010
- Slitrk5 deficiency impairs corticostriatal circuitry and leads to obsessive-compulsive–like behaviors in miceNature Medicine, 2010
- Decreased number of parvalbumin and cholinergic interneurons in the striatum of individuals with Tourette syndromeJournal of Comparative Neurology, 2009
- The pathophysiology of restricted repetitive behaviorJournal of Neurodevelopmental Disorders, 2009
- Cortico-striatal synaptic defects and OCD-like behaviours in Sapap3-mutant miceNature, 2007
- Nerve conduction velocity decrease and synaptic transmission alterations in caffeine-treated ratsNeurotoxicology and Teratology, 1994