Research ReportSympathetic premotor neurones project to and are influenced by neurones in the contralateral rostral ventrolateral medulla of the rat in vivo
Highlights
►Sympathetic premotor neurons in the RVLM receive inputs from the contralateral brainstem. ►Inputs are tonically active and predominantly inhibitory under basal conditions. ►We identified bulbospinal barosensitive neurons with projections to the contralateral RVLM. ►These data identify a novel source of tonic input to sympathetic premotor neurons.
Introduction
Increased sympathetic nerve activity is found in pathophysiological conditions and animal models of cardiovascular disease and is thought to be a key mechanism in the aetiology of hypertension (Guyenet, 2006, Mary and Stoker, 2003). The activity of vasomotor sympathetic nerves is dependent on excitatory drive from sympathetic premotor neurones in the brainstem and midbrain and, in particular, from neurones in the rostral ventrolateral medulla (RVLM: Dampney, 1994, Guyenet, 2006). Tonically active bulbospinal barosensitive cells within the RVLM, many of which synthesise adrenaline (Schreihofer and Guyenet, 1997), are thought to be a key relay in the generation of sympathetic tone. However, unravelling the factors responsible for their tonic activity remains a key research objective (Coote, 2007).
Two lines of evidence suggest a crucial role for populations of neurones that provide ongoing synaptic drive to sympathetic premotor neurones. Firstly, action potentials recorded in the adult rat in vivo are always preceded by excitatory synaptic potentials (see Dampney et al., 2003, Lipski et al., 1996, Lipski et al., 1998), suggesting that synaptic drive is essential for the generation of activity in these neurones. Secondly, when disaggregated from rhythmic drives such as respiratory and baroreceptive inputs, common rhythmic components occur in diverse sympathetic nerves (Barman and Kenney, 2007, Malpas, 1998) and in individual medullary neurones (Barman and Gebber, 1992), suggesting that inputs received by sympathetic premotor neurones also play an important role in the coordination of sympathetic nerve activity (see Barman and Gebber, 1989, Lipski et al., 2002).
However, the task of identifying the sources of tonic drive received by sympathetic premotor neurones has proceeded slowly. In the current study we examine the hypothesis that activity generated in the RVLM drives synaptic input to sympathetic premotor neurones in the contralateral RVLM and that tonically active inputs arising from commissural pathways may act to coordinate bulbospinal outputs. This hypothesis is based upon the observation that up to 25% of adrenaline-synthesising neurones in the RVLM project to targets in the contralateral RVLM (Card et al., 2006, Granata and Chang, 1994, Madden et al., 1999), although the function of such projections has not yet been examined.
The experimental aims of the current study are: 1. To determine whether activation of neurones in the pressor region of the RVLM alters the behaviour of functionally identified sympathetic premotor neurones recorded in the contralateral RVLM in vivo. 2. To compare the effects evoked by chemical and electrical activation of the contralateral RVLM. 3. To determine whether commissural inputs contribute to the activity of sympathetic premotor neurones under steady-state conditions.
Section snippets
Results
Recordings were made in the left side of the RVLM from 24 spontaneously active (median discharge rate: 11.7 Hz (range 0.5–47 Hz)) neurones in 20 rats. All were confirmed bulbospinal (median conduction velocity: 3.4 m.s− 1 (range 1–13.3 m.s− 1)) and barosensitive, satisfying the criteria for classification as sympathetic premotor neurones (Lipski et al., 1996). Recordings were made 1.6–2.1 mm left of the midline within 0.4 mm of the caudal pole of the facial nucleus. Drug microinjections in the right
Discussion
In this study we present four novel findings: 1. Activation of cell bodies in the pressor region of the RVLM drives excitatory and/or inhibitory synaptic inputs to sympathetic premotor neurones in the contralateral RVLM. 2. Electrical RVLM stimulation drives excitatory and inhibitory inputs that occur at different latencies from each other; excitatory responses occur over a range of latencies and jitters. 3. Inhibition of the RVLM disinhibits sympathetic premotor neurones in the contralateral
Experimental procedures
All experiments were approved by Macquarie University Animal Care and Ethics Committee and conformed to Australian guidelines.
Acknowledgments
Grants: Work in the Authors' laboratory is supported by the National Health & Medical Research Council of Australia (604002, 457080, 457069), the Australian Research Council (DP110102110), Garnett Passe & Rodney Williams Memorial Foundation, and Macquarie University.
Disclosures: None.
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