Nociceptive responses of midbrain dopaminergic neurones are modulated by the superior colliculus in the rat

Abstract

Midbrain dopaminergic neurones exhibit a short-latency phasic response to unexpected, biologically salient stimuli. In the rat, the superior colliculus is critical for relaying short-latency visual information to dopaminergic neurones. Since both collicular and dopaminergic neurones are also responsive to noxious stimuli, we examined whether the superior colliculus plays a more general role in the transmission of short-latency sensory information to the ventral midbrain. We therefore tested whether the superior colliculus is a critical relay for nociceptive input to midbrain dopaminergic neurones. Simultaneous recordings were made from collicular and dopaminergic neurones in the anesthetized rat, during the application of noxious stimuli (footshock). Most collicular neurones exhibited a short-latency, short duration excitation to footshock. The majority of dopaminergic neurones (92/110; 84%) also showed a short-latency phasic response to the stimulus. Of these, 79/92 (86%) responded with an initial inhibition and the remaining 14/92 (14%) responded with an excitation. Response latencies of dopaminergic neurones were reliably longer than those of collicular neurones. Tonic suppression of collicular activity by an intracollicular injection of the local anesthetic lidocaine reduced the latency, increased the duration but reduced the magnitude of the phasic inhibitory dopaminergic response. These changes were accompanied by a decrease in the baseline firing rate of dopaminergic neurones. Activation of the superior colliculus by the local injections of the GABA(A) antagonist bicuculline also reduced the latency of inhibitory nociceptive responses of dopaminergic neurones, which was accompanied by an increased in baseline dopaminergic firing. Aspiration of the ipsilateral superior colliculus failed to alter the nociceptive response characteristics of dopaminergic neurones although fewer nociceptive neurones were encountered after the lesions. Together these results suggest that the superior colliculus can modulate both the baseline activity of dopaminergic neurones and their phasic responses to noxious events. However, the superior colliculus is unlikely to be the primary source of nociceptive sensory input to the ventral midbrain.