Transient middle cerebral artery occlusion prevents habit formation in C57Bl/6J mice

Pathologies affecting the striatum (e.g., Parkinson’s and Huntington’s disease) can result in impaired habit learning abilities. Likewise, such impairments have also been observed after stroke affecting the middle cerebral artery territory (encompassing the striatum). However, habit learning has never been investigated in animal stroke models, for which it could be a reliable measure of cognitive deficits. We thus assessed the ability to learn a habitual sequence of lever-presses using operant conditioning in mice after MCAO, one of the most common stroke models. C57Bl/6J mice underwent MCAO or sham surgery. Sensorimotor functioning was assessed using the vertical pole test, rotarod and amphetamine-induced rotation test. Habit learning was evaluated using the operant serial order learning (SOL) task: mice had to perform a series of two consecutive lever-presses (i.e., left then right) to obtain a food reward. Lesion extents were finally determined using anti-NeuN immunohistochemistry. MCAO mice were significantly impaired in both the rotarod and vertical pole test, and displayed a significantly greater number of ipsilateral rotations after amphetamine administration. In the operant SOL task, MCAO committed more errors than sham; moreover, they did not show any significant increase in performance along the sessions. Histological analysis showed consistent striatal and cortical infarctions. The lack of habit learning ability in MCAO mice is congruent with both the literature investigating the effect of striatal lesion in animals and the symptomatology observed in human stroke patients. Habit learning could thus be regarded as a reliable measure of functional outcome after MCAO, in combination with test assessing sensory and motor aspects.