Morphological and physiological evidence of a synaptic connection between the lateral parabrachial nucleus and neurons in the A7 catecholamine cell group in rats

Abstract

BackgroundThe descending noradrenergic (NAergic) system is one of the important endogenous analgesia systems. It has been suggested that noxious stimuli could activate descending NAergic system; nevertheless, the underlying neuronal circuit remains unclear. As NAergic neurons in the A7 catecholamine cell group (A7) are a part of the descending NAergic system and the lateral parabrachial nucleus (LPB) is an important brainstem structure that relays ascending nociceptive signal, we aimed to test whether LPB neurons have direct synaptic contact with NAergic A7 neurons.ResultsStereotaxic injections of an anterograde tracer, biotinylated dextran-amine (BDA), were administered to LPB in rats. The BDA-labeled axonal terminals that have physical contacts with tyrosine hydroxylase-positive (presumed noadrenergic) neurons were identified in A7. Consistent with these morphological observations, the excitatory synaptic currents (EPSCs) were readily evoked in NAergic A7 neurons by extracellular stimulation of LPB. The EPSCs evoked by LPB stimulation were blocked by CNQX, a non-NMDA receptor blocker, and AP5, a selective NMDA receptor blocker, showing that LPB-A7 synaptic transmission is glutamatergic. Moreover, the amplitude of LPB-A7 EPSCs was significantly attenuated by DAMGO, a selective μ-opioid receptor agonist, which was associated with an increase in paired-pulse ratio.ConclusionsTaken together, the above results showed direct synaptic connections between LPB and A7 catecholamine cell group, the function of which is subject to presynaptic modulation by μ-opioid receptors.

Locus coeruleus anchors a trisynaptic circuit controlling fear-induced suppression of feeding

“…Our observations are consistent with recent work showing that activation of local GABAergic neurons in LC promotes feeding (Marino et al, 2020). Interestingly, PBN neurons also make excitatory, glutamatergic synapses on LC neurons (Liu et al, 2015), suggesting that the suppression of feeding might be augmented by a positive feedback loop between LC and PBN neurons.…”

“…Several potential polysynaptic pathways link CeA and LC. For example, CeA neurons innervate PBN neurons, which in turn innervate LC neurons (Liu et al, 2015). Although the previously reported electrophysiological coupling could be accounted for in this way, it is more difficult to reconcile the anatomical data using monosynaptic rabies virus mapping (msRVm) (Schwarz et al, 2015).…”

Sodium Leak Channel in Glutamatergic Neurons of the Lateral Parabrachial Nucleus Modulates Inflammatory Pain in Mice

“…Roeder et al [22] reported that activities of the rostral ventromedial medulla (RVM) evoked by nociceptive inputs were significantly attenuated by inactivation of PBL neurons. One study [18] showed that PBL sends excitatory glutamate to norepinephrine neurons in the A7 region of rats to participate in central analgesia and mediate pain inhibition at the spinal dorsal horn level. In the present study, chemogenetic activation or inhibition of PBL glutamatergic neurons reduced or increased basal pain thresholds, respectively, in mice, suggesting a close link between PBL glutamatergic neurons and pain sensation.…”

“…SNR-projecting PBL neurons can be activated by noxious stimuli [17]. In fact, most neurons in the PBL are glutamatergic [11,18]. A previous study [15] found that spinal cord projections to PBL are strictly glutamatergic.…”

The locus coeruleus contributes to the anorectic, nausea, and autonomic physiological effects of glucagon-like peptide-1

“…Sources of glutamatergic inputs previously described to excite LC NE neurons include the prefrontal cortex ( 84 ) and the paragigantocellular nucleus of the ventrolateral medulla ( 85 ), although other glutamatergic inputs should be considered ( 82 ). One candidate nuclei, the parabrachial nucleus (PBN), is a site of converging sensory and visceral malaise signals ( 86 ), sends direct glutamatergic projections to the LC ( 87 ), and expresses the GLP-1R ( 88 ). Other potential sources of glutamate include corticotropin-releasing factor neuron projections from the amygdala or orexin neuron projections from the hypothalamus, both of which co-release glutamate and have been shown to play a role in feeding behavior ( 89 , 90 ).…”