Behavioral and physiological roles of the striatal GABAergic interneuronal types

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The striatum is a central structure of the basal ganglia neural circuitry that mediates a variety of brain functions including motor control, motor learning, and reward-associated behavior. It contains some GABAergic interneuronal types that are different in their morphology and electrophysiological property. However, the difference in their behavioral and physiological roles remains unknown. In the present study, we addressed to study the roles of two kinds of straital GABAergic interneuronal types containing somatostatin (SST) or parvalbumin (PVA). We utilized immunotoxin cell targeting to eliminate the specific neuronal type from the neural circuitry and studied the resultant phenotypic changes. To eliminate the striatal GABAergic interneurons containing SST, we generated the mutant mice in which the human interleukin-2 receptor a-subunit (IL-2Rα) gene cassette was introduced into the mouse preprosomatostatin gene locus. These mice were injected intrastriatally with the recombinant immunotoxin, and the number of target neurons were reduced in the mutants. Phenotypic analysis of the mutants indicated that the SST-containing GABAergic interneurons play an important role in suppression of spontaneous motor behavior. In addition, to eliminate the straital GABAergic interneurons containing PVA we tried to produce the mutant mice in which the human IL-2Rα cassette was introduced into the mouse PVA gene locus. The knock-in targeting vector was introduced into embryonic stem (ES) cells, and the cells carrying the targeted mutation were screened with PCR and southern blot hybridization. We succeeded in obtaining multiple ES cells carrying the targeted mutation. Using these cells we are planning to generate the knock-in mutant mice and perform immunotoxin cell targeting to elucidate the behavioral and physiological roles of the striatal GABAergic interneurons containing PVA.