Reduced Axon Calibre in the Associative Striatum of the Sapap3 Knockout Mouse.

Eliana Lousada,Julien Cohen-Adad,Mathieu Boudreau,Eric Burguière,Christiane Schreiweis,Brahim Nait Oumesmar

doi: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.

Highlights

Repetitive, ritualistic actions are a core feature of animal behaviour, including humans, which allow for efficient learning and automatisation of behaviour [1,2,3]
Axon Calibre Is Diminished in the Associative but Not in the Sensorimotor Striatum of Sapap3-KO Mice
Taking advantage of a deep learning algorithm, AxonDeepSeg, which is capable of automatically, rapidly, and accurately segmenting and measuring myelinated axons from electron microscopy data in an unbiased manner [49] (Figure 1b), we assessed the properties of approximately 150 axons per region and animal

Summary

Introduction

Repetitive, ritualistic actions are a core feature of animal behaviour, including humans, which allow for efficient learning and automatisation of behaviour [1,2,3]. Cortico-striatal circuits are the principal anatomical region that underlies the development of RB [4,5]. These circuits follow a parallel, mostly segregated, structural–functional organisation of limbic, associative, and sensorimotor pathways of information processing [6,7,8]. The loops, related to these compulsive-like RBs, are the associative cortico-striatal circuits [15,16,17,18,19] Despite this putative anatomical segregation of different types of RBs, a great percentage of comorbidity has been reported between TS and OCD patients, which points towards the existence of common anatomo-functional ground [20,21,22,23]

Methods

Results

Conclusion