Lesion of striatal patches disrupts habitual behaviors and increases behavioral variability

Abstract

14Habits are automated behaviors that are insensitive to changes in behavioral outcomes. Habitual responding is 15 thought to be mediated by striatum, with medial striatum guiding goal-directed action and lateral striatum promoting 16 habits. However, interspersed throughout the striatum are neurochemically differing subcompartments known as 17 patches, which are characterized by distinct molecular profiles relative to the surrounding matrix tissue. These 18 structures have been thoroughly characterized neurochemically and anatomically, but little is known regarding their 19 function. Patches have been shown to be selectively activated during inflexible motor stereotypies elicited by 20 stimulants, suggesting that patches may subserve habitual behaviors. To explore this possibility, we utilized 21 transgenic mice (Sepw1 NP67) expressing Cre recombinase in striatal patches to target these neurons for selective 22 ablation with a virus driving Cre-dependent expression of caspase 3. Mice were then trained to press a lever for 23 sucrose rewards on a variable interval schedule to elicit habitual responding. Mice were not impaired on the 24 acquisition of this task, but lesioning striatal patches disrupted behavioral stability across training and lesioned mice 25 utilized a more goal-directed behavioral strategy during training. Similarly, when mice were forced to omit 26 responses to receive sucrose rewards, habitual responding was impaired in lesioned mice. To rule out effects of 27 lesion on motor behaviors, mice were then tested for impairments in motor learning on a rotarod and locomotion in October 15, 2019 2/22 28 an open field. We found that patch lesions specifically impaired initial performance on the rotarod without 29 modifying locomotor behaviors in open field. This work indicates that patches promote behavioral stability and 30 habitual responding, adding to a growing literature implicating striatal patches in stimulus-response behaviors. 31 32 33