Behavioral changes induced by striatal interneurons ablation

COLL C; BRAZ BY; BECCARIA JP; BELFORTE, J.E.; MURER MG

cordoba

Congreso; XXXIII CONGRESO ANUAL SAN 2018; 2018

Sociedad Argentina de Investigacón en Neurociencias

Corticostriatal dysfunction is involved in Parkinson's disease and Tourette syndrome(TS), amongother neurop sychiatric disorders. There are studies showing a reduced number of multiple striatalinterneurons (SIs) types in the brain of TS patients. In a previous study where we induced aselective ablation of striatal cholinergic interneurons in the mouse, we obse rved perseverativebehaviors reminiscent of those observed in TSand related disorders, but we did not observe tics.In order to reproduce more closely the striatal changes observed in TS, we aimed to perform acombined ablation of striatal cholinergic and GABAergic interneurons by directing the expressionof the human diphtheria toxin receptor to neurons that express Nkx2.1 before differentiating intodifferent types of SIs. By administering diphtheria toxin (DT) into the striatum we obtained aselective ab lation of Nkx2.1 positive interneurons. Mice treated with extensive SIs ablationsdeveloped unwilling and abnormal movements, alterations oflocomotion and posture, and usuallydied during the first week after DT injection. Mice with restricted SIs ablation s showed unwillingmovements that did not progress and are being studied with a battery of behavioral tests.Altogether our data suggest a putative mechanism for the involuntary movements observed inpatients with ?benign hereditary chorea? caused by mutat ions of the Nkx2.1 gene and that tics inTS may be caused by combined dysfunction of multiple SIs types.