Abstract
Many dopaminergic neurons exhibit a short-latency response to noxious stimuli, the source of which is unknown. Here we report that the nociceptive-recipient parabrachial nucleus appears to be a critical link in the transmission of pain related information to dopaminergic neurons. Injections of retrograde tracer into the substantia nigra pars compacta of the rat labelled neurons in both the lateral and medial parts of the parabrachial nucleus, and intra-parabrachial injections of anterograde tracers revealed robust projections to the pars compacta and ventral tegmental area. Axonal boutons were seen in close association with tyrosine hydroxylase-positive (presumed dopaminergic) and negative elements in these regions. Simultaneous extracellular recordings were made from parabrachial and dopaminergic neurons in the anaesthetized rat, during the application of noxious footshock. Parabrachial neurons exhibited a short-latency, short duration excitation to footshock while dopaminergic neurons exhibited a short-latency inhibition. Response latencies of dopaminergic neurons were reliably longer than those of parabrachial neurons. Intra-parabrachial injections of the local anasethetic lidocaine or the GABAA receptor antagonist muscimol reduced tonic parabrachial activity and the amplitude (and in the case of lidocaine, duration) of the phasic response to footshock. Suppression of parabrachial activity with lidocaine reduced the baseline firing rate of dopaminergic neurons, while both lidocaine and muscimol reduced the amplitude of the phasic inhibitory response to footshock, in the case of lidocaine sometimes abolishing it altogether. Considered together, these results suggest that the parabrachial nucleus is an important source of short-latency nociceptive input to the dopaminergic neurons.
Highlights
The source of the afferent inputs which relay pain-related information to DA neurons is still uncertain, during our retrograde anatomical work on the tectonigral projection, which involved the placement of tracer injections in the substantia nigra pars compacta (SNPc), we noticed numerous retrogradely labelled cells in the mesopontine parabrachial nucleus (PBN)
We have recently shown that a subcortical visual structure, the midbrain superior colliculus (SC), is the primary, if not the exclusive, source of short-latency visual input to midbrain DA neurons (Comoli et al, 2003; Dommett et al, 2005), possibly mediated in part by the tectonigral projection—a direct projection from the SC to the substantia nigra pars compacta (SNPc) and ventral tegmental area (VTA), which innervates DA neurons in these regions (Comoli et al, 2003; McHaffie et al, 2006; May et al, 2009)
To confirm our previous informal observation that injections of retrograde tracer into the SNPc give rise to labelled cells in the PBN, small quantities of the retrograde tracer fluorogold were injected into the SNPc (Fig. 1A) and VTA
Summary
The source of the afferent inputs which relay pain-related information to DA neurons is still uncertain, during our retrograde anatomical work on the tectonigral projection, which involved the placement of tracer injections in the SNPc, we noticed numerous retrogradely labelled cells in the mesopontine parabrachial nucleus (PBN). The general distribution of retrogradely labelled cells in the PBN was very similar following an injection in the lateral part of the SNPc, the central part of the SNPc, or VTA, and the projection appears to innervate the whole dopamine containing region of the ventral midbrain, but exhibits little topography.
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