演題番号 : P1-m17
西澤 佳代 / Kayo Nishizawa:1 深堀 良二 / Ryoji Fukabori:1 甲斐 信行 / Nobuyuki Kai:1 筒井 雄二 / Yuji Tsutsui:2 内ヶ島 基政 / Motokazu Uchigashima:3 渡辺 雅彦 / Masahiko Watanebe:3 塩田 明 / Akira Shiota:4 上田 正次 / Masatsugu Ueda:4 小林 和人 / Kazuto Kobayashi:1
1:福島県立医科大学・医学部・生体機能研究部門 / Department of Molecular Genetics, Fukushima Medical University School of Medicine 2:福大・共生理工・人間支援 / Dept Human Support System, Fukushima University 3:北大・医・解剖発生 / Dept of Anatomy and Embryology, Hokkaido University Graduate School of Medicine 4:（株）フェニックスバイオ / PhoenixBio Co., Ltd.
The dorsal striatum plays an important role for the learning processes of instrumental actions, such as goal-directed behavior and stimulus-response association. Striatal projections are composed of two subpopulations of GABAergic medium spiny neurons that constitute the direct (striatonigral) and indirect (striatopallidal) pathways. It remains unclear how these two pathways contribute to the mechanism underlying instrumental learning. Immunotoxin-mediated cell targeting is a transgenic technique to eliminate specific cell type from a complex neural circuitry. Here, we generated transgenic rats that expressed the human interleukin-2 receptor alpha-subunit under the control of the gene encoding dopamine D2 receptor (D2R), which is known to be localized in the striatopallidal neurons. Intrastriatal immunotoxin treatment induced a selective elimination of the striatopallidal neurons while persisting normally the number of striatonigral neurons. We tested the influence of striatopallidal elimination on the performance of an auditory discrimination task. Rats were required to press one of the two levers dependent on the different auditory stimuli of 2000 and 8000 Hz for obtaining a reward. After the acquisition of the task, we injected the immunotoxin into the dorsal striatum of rats. In the injected transgenic rats, the correct response ratio was significantly reduced on post-operative day7-10, whereas speed of correct response and omission ratio of response were not changed in these rats. Our results suggest that the striatopallidal neurons are necessary for controlling the accuracy of response selection in the conditional discrimination task.