MIM-Deficient Mice Exhibit Anatomical Changes in Dendritic Spines, Cortex Volume and Brain Ventricles, and Functional Changes in Motor Coordination and Learning

Rimante Minkeviciene; Iryna Hlushchenko; Anaïs Virenque; Lauri Lahti; Pushpa Khanal; Tuomas Rauramaa; Arto Koistinen; Ville Leinonen; Francesco M Noe; Pirta Hotulainen

doi:10.3389/fnmol.2019.00276

MIM-Deficient Mice Exhibit Anatomical Changes in Dendritic Spines, Cortex Volume and Brain Ventricles, and Functional Changes in Motor Coordination and Learning

Front Mol Neurosci. 2019 Nov 15:12:276. doi: 10.3389/fnmol.2019.00276. eCollection 2019.

Authors

Rimante Minkeviciene¹, Iryna Hlushchenko¹, Anaïs Virenque^{2

3}, Lauri Lahti⁴, Pushpa Khanal^{1

3}, Tuomas Rauramaa⁵, Arto Koistinen⁶, Ville Leinonen^{7

8

9}, Francesco M Noe^{2

3}, Pirta Hotulainen¹

Affiliations

¹ Minerva Foundation Institute for Medical Research, Helsinki, Finland.
² A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
³ HiLIFE - Neuroscience Center, University of Helsinki, Helsinki, Finland.
⁴ Department of Computer Science, Aalto University School of Science, Espoo, Finland.
⁵ Department of Clinical Pathology, Kuopio University Hospital, University of Eastern Finland, Kuopio, Finland.
⁶ SIB Labs Infrastructure Unit, University of Eastern Finland, Kuopio, Finland.
⁷ Neurosurgery of NeuroCenter, Kuopio University Hospital, University of Eastern Finland (UEF), Kuopio, Finland.
⁸ Research Unit of Clinical Neuroscience, University of Oulu, Oulu, Finland.
⁹ Department of Neurosurgery, MRC Oulu, Oulu University Hospital, Oulu, Finland.

Abstract

In this study, we performed a comprehensive behavioral and anatomical analysis of the Missing in Metastasis (Mtss1/MIM) knockout (KO) mouse brain. We also analyzed the expression of MIM in different brain regions at different ages. MIM is an I-BAR containing membrane curving protein, shown to be involved in dendritic spine initiation and dendritic branching in Purkinje cells in the cerebellum. Behavioral analysis of MIM KO mice revealed defects in both learning and reverse-learning, alterations in anxiety levels and reduced dominant behavior, and confirmed the previously described deficiency in motor coordination and pre-pulse inhibition. Anatomically, we observed enlarged brain ventricles and decreased cortical volume. Although MIM expression was relatively low in hippocampus after early development, hippocampal pyramidal neurons exhibited reduced density of thin and stubby dendritic spines. Learning deficiencies can be connected to all detected anatomical changes. Both behavioral and anatomical findings are typical for schizophrenia mouse models.

Keywords: anxiety; brain ventricles; dendritic spines; learning; motor coordination.