Effects of transient inactivation of the subthalamic nucleus by local muscimol and APV infusions on performance on the five-choice serial reaction time task in rats

Abstract

Within the basal ganglia circuitry, recent conceptions of the subthalamic nucleus are that it fulfils integrative functions. We have previously shown that bilateral excitotoxic lesions of the subthalamic nucleus induce behavioural deficits in a five-choice serial reaction time task in the rat, consistent with attentional impairments and suggesting important roles of this basal ganglia structure in mechanisms of behavioural control. In the present study, we tested the effects of (i) blocking its excitatory inputs (originating mainly in the cerebral cortex and the parafascicular nucleus of the thalamus) via the NMDA receptors and (ii) stimulating its GABA receptors to mimick the influence of its inhibitory inputs (mainly from the globus pallidus). Bilateral microinfusions of APV (NMDA receptor antagonist) or muscimol (GABA-A receptor agonist) into the subthalamic nucleus were administered to rats trained in the same five-choice serial reaction time task. Both APV (0.125–0.5 μg) and muscimol (1–3 ng) reduced choice accuracy, slowed correct responses and increased omissions and perseverative responses. Premature responses tended to increase after APV but decrease after muscimol. Increased perseverations at the food magazine occurred only after muscimol infusions. These results reproduce many of the effects of lesions of the STN and are consistent with an integrative role for this structure in pallidal and thalamo-cortical processing.