Dopamine effects on identified rat vagal motoneurons

Abstract

Catecholaminergic neurons of the A2 area play a prominent role in brain stem vagal circuits. It is not clear, however, whether these neurons are noradrenergic or adrenergic, i.e., display tyrosine hydroxylase (TH) and dopamine-β-hydroxylase (DβH) immunoreactivity (-IR) or dopaminergic (i.e., TH-but not DβH-IR). Our aims were to investigate whether a subpopulation of neurons in the A2 area was dopaminergic and, if so, to investigate the effects of dopamine (DA) on the membrane of gastric-projecting vagal motoneurons. We observed that although the majority of A2 neurons were both TH-and DβH-IR, a small percentage of nucleus tractus solitarius neurons were TH-IR only, suggesting that DA itself may play role in these circuits. Whole cell recordings from thin brain stem slices showed that 71% of identified gastric-projecting motoneurons responded to DA (1-300 µM) with either an excitation (28%) or an inhibition (43%) of the membrane; the remaining 29% of the neurons were unresponsive. The DA-induced depolarization was mimicked by SK 38393 and prevented by pretreatment with SCH 23390. Conversely, the DA-induced inhibition was mimicked by bromoergocryptine and prevented by pretreatment with L741626. When tested on the same neuron, the effects of DA and NE were not always similar. In fact, in neurons in which DA induced a membrane depolarization, 77% were inhibited by NE, whereas 75% of neurons unresponsive to DA were inhibited by NE. Our data suggest that DA modulates the membrane properties of gastric-projecting motoneurons via D1-and D2-like receptors, and DA may play different roles than norepinephrine in brain stem vagal circuits. Keywords brain stem; electrophysiology; gastricThe dorsal vagal complex (DVC), i.e., the nucleus tractus solitarius (NTS), the dorsal motor nucleus of the vagus (DMV), and the area postrema (AP), plays an important role in the control of homeostatic and autonomic functions, including the modulation of functions in the gastrointestinal (GI) tract. Sensory information from the GI tract is received and integrated by NTS neurons where it is modulated and transferred to, among other areas, the preganglionic neurons of the DMV; DMV neurons then provide a regulated efferent motor vagal outflow to the GI tract (reviewed recently in Refs. 38,39).A vast array of neurotransmitters are present in the DVC; by modulating the neuronal membrane and/or the synaptic connections between the tractus solitarius, the NTS, and the DMV, each neurotransmitter may contribute to the fine tuning of selected circuits devoted to specific functions (reviewed recently in Ref. 33). Among these neurotransmitters catecholamines, originating either from neurons in the A6, A5, A2, and A1/C1 areas and/or

Gastric dysregulation induced by microinjection of 6-OHDA in the substantia nigra pars compacta of rats is determined by alterations in the brain-gut axis

“…In particular, we distinguished three separate populations of gastric-projecting DMV neurons in response to brainstem perfusion with dopamine. The majority of responsive neurons were inhibited via activation of D2-like receptors, whereas smaller subpopulations of DMV neurons were either excited via activation of D1-like receptors or unresponsive to dopamine administration (60). Similar responses of the DMV membrane were obtained upon perfusion of norepinephrine, which excited the vast majority and inhibited a small minority of responsive neurons (32), as described previously in unidentified brainstem vagal neurons (16).…”

Enteric Dysfunctions in Experimental Parkinsons Disease: Alterations of Excitatory Cholinergic Neurotransmission Regulating Colonic Motility in Rats

“…In this regard, increasing evidence suggests that the DMV, which is known to provide most of the parasympathetic innervation to the GI tract (Jellinger, 1987), is one of the central nervous system sites affected by PD pathology at its early stage (Del Tredici et al, 2002). Indeed, neurochemical changes affecting the ENS, after central dopaminergic denervation, have been shown to depend on alterations of the DMV, which is regulated by brainstem dopaminergic circuitries and represents a prominent target of PD-related neurodegenerative processes (Braak et al, 2003(Braak et al, , 2004Zheng and Travagli, 2007;Zheng et al, 2011). In this regard, the vagus nerve has been proposed to play a crucial role in the regulation of inflammatory responses, a function also referred to as the "cholinergic anti-inflammatory pathway" (Matteoli and Boeckxstaens, 2013).…”

The role of vagal neurocircuits in the regulation of nausea and vomiting

“…Under normal conditions, the activity of DMV neurons that innervate the GI tract is controlled by a tonic GABAergic input from the NTS (Sivarao et al, 1998; Travagli et al, 1991, 2006). The activity of synaptic inputs impinging upon DMV neurons, hence the excitability and efferent output of DMV neurons, can be modulated by numerous neurotransmitters and neuromodulators, including those implicated in emetic reflexes such as, for example, opioid peptides (Browning et al, 2004, 2002), serotonin (Browning and Travagli, 1999; Mussa et al, 2008; Travagli and Gillis, 1995), endocannabinoids (Derbenev et al, 2004; Glatzer and Smith, 2005), tachykinins (Ladic and Buchan, 1996; Le et al, 2008; Lewis and Travagli, 2001) and dopamine (Cai et al, 2013; Zheng and Travagli, 2007). Activity within vagal efferent pathways during emetic reflexes results in a large retropulsive wave of intestinal motility accompanied by gastric contraction.…”