Immp2l knockdown in male mice increases stimulus-driven instrumental behaviour but does not alter goal-directed learning or neuron density in cortico-striatal circuits in a model of Tourette syndrome and autism spectrum disorder

• DOI: 10.1016/j.bbr.2023.114610
• Publication Date: 2023-08-02T15:21:57Z
• Authors: Beatrice K. Leung; Sam Merlin; Adam K. Walker; Adam J. Lawther; George Paxinos; Valsamma Eapen; Raymond Clarke; Bernard W. Balleine; Teri M. Furlong
• Keywords: Stimulus (psychology)

Cortico-striatal neurocircuits mediate goal-directed and habitual actions which are necessary for adaptive behaviour. It has recently been proposed that some of the core symptoms autism spectrum disorder (ASD) Gilles de la Tourette syndrome (GTS), such as tics other repetitive behaviours, may emerge because imbalances in these neurocircuits. We have developed a model ASD GTS by knocking down Immp2l, mitochondrial gene frequently associated with disorders. The current study sought to determine whether Immp2l knockdown (KD) male mice alters flexible, goal- or cue- driven behaviour using procedures specifically designed examine response-outcome stimulus-response associations, underlie behaviour, respectively. Whether KD neuron density cortico-striatal known regulate behaviours was also examined. wild type-like (WT) were trained on Pavlovian instrumental learning where auditory cues predicted food delivery lever-press responses earned outcome. demonstrated not changed compared WT mice, sensitive changes value outcome, contingency reversal degradation. There no difference capacity form following extending training action. However, more responsive stimuli paired indicated non-specific increase lever response rates during Pavlovian-to-instrumental transfer. Finally, there alterations striatum any prefrontal cortex limbic brain structures Thus, suggests is learned maladaptive goal stimulus GTS, but it contribute increased external drive Alterations stimulus-driven could potentially influence expression suggesting genetic GTS. Given this first application battery mouse an important initial step determining contribution risk-genes versus should be broadly applied rodent models future.