GABAergic mechanisms in the cat red nucleus: effects of intracerebral microinjections of muscimol or bicuculline on a conditioned motor task

Abstract

Interneurons in the Red Nucleus (RN) are known to be under cortical control and to exert an inhibitory action, mediated by GABAergic mechanisms, on the main output towards the spinal cord. The effects of discrete injections of a GABA receptor agonist (muscimol) or an antagonist (bicuculline) in the Red Nucleus were tested on a motor task performed by seven cats. The subjects were trained to release a lever with a flexion movement of the forelimb controlled by a reaction time (RT) paradigm. Muscimol as well as bicuculline increased RTs in a dose-dependent manner at doses below 100 ng. However the parameters of the force exerted on the lever were differentially altered by the two drugs. Muscimol increased RTs by slowing down the force change preceding movement as well as slightly delaying its latency. While bicuculline increased drastically the force change latency. It could also speed up the force change velocity for low doses. At higher doses (up to 500 ng) both drugs produced an arrest of the performance either associated with anxiety signs (bicuculline) or dystonic movements of the head followed by body rotations (muscimol). The strong motor impairments as well as the disruption of the conditioned performances following muscimol or bicuculline microinjection in the RN suggest an important functional role for GABAergic interneurons. Under the control of cortical afferences they can modulate rubrospinal activity and participate in the triggering of a conditioned movement.