Evidence that projections from substantia innominata to zona incerta and mesencephalic locomotor region contribute to locomotor activity.

A series of anatomical, electrophysiological and behavioral experiments was carried out in the rat to investigate the possible functional significance of a recently demonstrated neural pathway from the substantia innominata of the subpallidal forebrain to the mesencephalic locomotor region. Following injections of the anterogradely transported lectin PHA into the substantia innominata labeled fibers with terminal boutons were observed in the zona incerta, dorsal to the medial part of the subthalamic nucleus, and some appeared to continue on to the pedunculopontine nucleus. Electrophysiological recordings of action potentials were made from neurons in the substantia innominata and some of these neurons were activated antidromically by single-pulse stimulation of the zona incerta and/or by single-pulse stimulation of the pedunculopontine nucleus as well. Neurons in the zona incerta responded orthodromically to stimulation of the substantia innominata. Locomotor activity was initiated by injecting picrotoxin, a GABA antagonist, unilaterally into the substantia innominata through chronic cannulae, as reported previously. This picrotoxin-initiated locomotor activity was reduced significantly when procaine (a neuronal blocker) was injected into the ipsilateral zona incerta. Injecting procaine into the contralateral zona incerta had little or no effect on the picrotoxin-initiated locomotor activity. Taken together these observations suggest the tentative working hypothesis that projections from the substantia innominata to the zona incerta as well as the pedunculopontine nucleus may contribute to the locomotor component of adaptive behaviors resulting from limbic forebrain integrative activities, an hypothesis that can now be investigated further.