Cat's medullary reticulospinal and subnucleus reticularis dorsalis noxious neurons form a coupled neural circuit through collaterals of descending axons

Abstract

Animals and human beings sense and react to real/potential dangerous stimuli. However, the supraspinal mechanisms relating noxious sensing and nocifensive behavior are mostly unknown. The collateralization and spatial organization of interrelated neurons are important determinants of coordinated network function. Here we electrophysiologically studied medial medullary reticulospinal neurons (mMRF-RSNs) antidromically identified from the cervical cord of anesthetized cats and found that 1) more than 40% (79/183) of the sampled mMRF-RSNs emitted bifurcating axons running within the dorsolateral (DLF) and ventromedial (VMF) ipsilateral fascicles; 2) more than 50% (78/151) of the tested mMRF-RSNs with axons running in the VMF collateralized to the subnucleus reticularis dorsalis (SRD) that also sent ipsilateral descending fibers bifurcating within the DLF and the VMF. This percentage of mMRF collateralization to the SRD increased to more than 81% (53/65) when considering the subpopulation of mMRF-RSNs responsive to noxiously heating the skin; 3) reciprocal monosynaptic excitatory relationships were electrophysiologically demonstrated between noxious sensitive mMRF-RSNs and SRD cells; and 4) injection of the anterograde tracer Phaseolus vulgaris leucoagglutinin evidenced mMRF to SRD and SRD to mMRF projections contacting the soma and proximal dendrites. The data demonstrated a SRD-mMRF network interconnected mainly through collaterals of descending axons running within the VMF, with the subset of noxious sensitive cells forming a reverberating circuit probably amplifying mutual outputs simultaneously regulating motor activity and spinal noxious afferent input. The results provide evidence that noxious stimulation positively engages a reticular SRD-mMRF-SRD network involved in pain-sensory-to-motor transformation and modulation.

Reticular Formation and Pain: The Past and the Future

“…The DRt is also a major integrative relay for descending nociceptive modulation from several brain areas including the cortex (Zhang et al, 2005 ), the hypothalamus (Amorim et al, 2015 ) and the brainstem (Martins et al, 2013 ; Velo et al, 2013 ; Leiras et al, 2016 ). The DRt was shown to relay descending pain facilitation from the anterior cingulate cortex (ACC; Zhang et al, 2005 ).…”

“…The DRt is also involved in a network of reciprocal connections established between collaterals of DRt and medial medullary reticular spinally-projecting neurons (Figure 2 ; Leiras et al, 2016 ). Medial medullary reticular neurons are involved in nociceptive and escape motor responses (Casey and Morrow, 1989 ), it is therefore likely that the DRt might integrate noxious sensing and nocifensive behavior through the collaterals of descending axons with medullary reticulospinal neurons.…”

Diversity of reticulospinal systems in mammals

“…The DPGi, for instance, has been implicated in the regulation of sleep/wake cycle through its reticulo-reticular connections [37,[24][25][26][27][28] but the participation of the DPGi RS neurons in this context has not been clarified. Similarly, the RS neurons in the MdD, a key region for the transmission and modulation of pain often referred to as subnucleus reticularis dorsalis or SRD, may produce pain-related motor reactions by sending axon collaterals to the RS neurons in the Gi [38]. RS neurons in PCRt and IRt have direct connections with triceps motoneurons [39] and could therefore be mediate forelimb extension but it remains unclear in which behavioral contexts.…”