Nigral glutamatergic neurons control the speed of locomotion

Abstract

The mesencephalic locomotor region (MLR) plays a crucial role in locomotor control. In vertebrates, stimulation of the MLR at increasing intensities elicits locomotion of growing speed. This effect has been presumed to result from higher brain inputs activating the MLR like a dimmer switch. Here, we show in lampreys (Petromyzon marinus) of either sex that incremental stimulation of a region homologous to the mammalian substantia nigra pars compacta (SNc) evokes increasing activation of MLR cells with a graded increase in the frequency of locomotor movements. Neurons co-storing glutamate and dopamine were found to project from the primal SNc to the MLR. Blockade of glutamatergic transmission largely diminished MLR cell responses and locomotion. Local blockade of D1 receptors in the MLR decreased locomotor frequency, but did not disrupt the SNc-evoked graded control of locomotion. Our findings revealed the presence of a glutamatergic input to the MLR originating from the primal SNc that evokes graded locomotor movements.