Stimulation of the pedunculopontine tegmental nucleus in the rat produces burst firing in A9 dopaminergic neurons

Stimulation of the medial prefrontal cortex in the rat produces events in m idbrain dopaminergic neurons which resemble natural bursts, and which are c losely time-locked to the stimulation, albeit with a very long latency. As a consequence, we have previously argued that such bursts are polysynaptica lly generated via more proximal excitatory amino acidergic afferents, arisi ng, for example, from the pedunculopontine tegmental nucleus. In the presen t study, single-pulse electrical stimulation applied to this nucleus (and o ther sites in the rostral pens) was found to elicit responses in the majori ty of substantia nigra (A9) dopaminergic neurons. Responses usually consist ed of long-latency, long-duration excitations or inhibition-excitations. Th irty-seven percent of responses (currents combined) elicited by stimulation of the pedunculopontine tegmental nucleus contained time-locked bursts, th e bursts being embedded in the long-duration excitatory phases of excitatio n and inhibition-excitation responses. Stimulation sites located within 0.5 mm of the pedunculopontine tegmental nucleus were also effective at elicit ing time-locked bursts (although less so than sites located in the nucleus itself), whereas more distal sites were virtually ineffective. For response s containing time-locked bursts, a higher percentage of stimulations produc ed a burst when the response was elicited from within the pedunculopontine tegmental nucleus than when it was elicited from outside: the bursts themse lves having a very long latency (median of 96.2 ms; shorter than that of me dial prefrontal cortex-induced bursts). Finally, although there was no diff erence in the distribution within the substantia nigra pars compacta of cel ls which exhibited time locked bursting and those which did not, stimulatio n-induced bursts were elicited more frequently in dopaminergic neurons whic h were classified as "bursting" on the basis of their basal activity. The pedunculopontine tegmental nucleus appears to be a critical locus in th e rostral pens for the elicitation of time-locked bursts in A9 dopaminergic neurons. Since time-locked bursts were more often elicited from cells whic h exhibited bursting under basal conditions, this suggests that rostral pon tine sites, in particular the pedunculopontine tegmental nucleus, may play a role in the natural burst activity of dopaminergic neurons. Given that bu rsts in dopaminergic neurons are generated in response to primary and secon dary reinforcers, the projection from the pedunculopontine tegmental nucleu s could be one means by which motivationally relevant information (arising, for example, from the medial prefrontal cortex) reaches these cells. (C) 1 999 IBRO. Published by Elsevier Science Ltd.