P.1.b.006 Role of striatal cholinergic interneurons in attention during learning in the rat

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Aim of this study: Attentional set-shifting is a kind of flexible behaviour in which attention shifts from one stimulus dimension to another stimulus dimension. Many pieces of evidence suggest that the striatum plays a role in the set-shifting [1,2]. We investigated the hypothesis that cholinergic interneurons (CINs) play a role in such flexible behavior, using a set-shifting paradigm and immunotoxin-induced lesions of the CINs. Materials and Methods: We used Long-Evans rats (n = 42) weighing 250–300 g on arrival. All procedures were approved by OIST Animal Care and Use Committee. Control and lesion groups were prepared for each of three behavioural conditions (n = 7 in each group). Immunotoxin (anti-cholineacetyl transferase saporin) was bilaterally injected into the dorsomedial striatum (DMS), causing a specific lesion of the CINs while leaving other types of cells intact [3]. After recovery, instrumental conditioning was commenced in operant chambers. Throughout the experiments, each daily session consisted of 80 trials. In the initial 4 sessions, both left and right levers were inserted and animals learnt to press either the left or right lever to obtain a sucrose pellet, during which the light stimulus was differently presented as follows: condition 1, no light given; condition 2, a light presented always above the correct lever; condition 3, a light presented randomly on either side. In the subsequent 10 sessions, the light stimulus was randomly presented on either the left or right lever and animals learnt to choose a correct lever cued by the light (visual-cue learning). These procedures enabled us to examine different types of attentional shift to the light during visual-cue learning based on attention to: a novel stimulus; a previously relevant stimulus; or a previously irrelevant stimulus. Percentages of correct responses in each session were analyzed. After completion of the behavioural experiments, we analyzed the lesion histologically. Results: Comparing the percentages of correct responses in visual-cue learning between control groups showed that learning was faster in the condition when the light cue was previously relevant than when there was no light cue or the light was previously irrelevant. Lesions of the CINs impaired switching during visual-cue learning in the condition when the light cue was previously irrelevant, which required the animals to attend to a previously ignored stimulus. On the other hand, the lesion did not have a prominent effect on visual-cue learning under previously no-cue or relevant-cue conditions. Lesioned rats finally acquired visual-cue learning at 10th session in all conditions. Conclusions: The present results suggest that the CINs in DMS play an important role in attending to a previously irrelevant stimulus during set-shifting. However, these neurons do not strongly contribute to attentional processes when attending to a previously relevant or a novel stimulus for shifting attentional set during learning.