Disinhibition of the rostral ventral medulla increases blood pressure and Fos expression in bulbospinal neurons

J.B. Minson, I.j. Llewellyn-Smith, L.f. Arnolda, P.M. Pilowsky, J.R. Oliver, J.P. Chalmers
Brain Research 646 (1994)

The rostral ventral medulla (RVM) contains neurons that project to the spinal cord, and are the major source of drive to the sympathetic neurons of the spinal cord. These tonically active bulbospinal neurons are the major source of sympathetic control of arterial pressure. The activity of these neurons is regulated by inhibitory inputs that originate in the caudal ventrolateral medulla (CVLM) and utilize GABA as the neurotransmitter. This inhibitory pathway is likely to be the critical inhibitory link in the baroreceptor reflex control of efferent sympathetic nerve activity. This study tests whether inhibition of this GABA-mediated pathway will result in increased activation of the RVM.

 In this study, the spinal cords of 10 male rats were injected with Cholera toxin B (CTB), which is a tracer that travels retrogradely from the synapse at the preganglionic injection site to the cell body in the brain that innervates the preganglionic neuron. After recovering from the injection for 3 days, the rats underwent injection of either vehicle (control) or muscimol into the CVLM. Muscimol (GABA_A receptor agonist) was injected to inhibit neuronal activity at the CVLM, thus disinhibiting the RVLM. Blood pressure and heart rate were recorded for 120 minutes post-injection from each rat. Following these recordings, rats were perfused and their tissue was immunohistochemically processed for Fos and CTB. Fos is a marker for neuronal activation and is used in this study to determine the activity of the rat RVLM post-Muscimol injection. Essentially, if a neuron became activated enough, then it would express Fos. Finally, Fos- and CTB-positive neurons were counted via light microscopy.

 Both the heart rate and the blood pressure increased in response to muscimol injection (256+17 BPM to 428+19 BPM, 103+2 mmHg to 178+6 mmHg, respectively). More neurons positive for both Fos and CTB were observed in the RVM of the muscimol-injected rats than those of the vehicle-injected rats. Muscimol injected rats demonstrated a 22+1.9% increase in Fos+CTB neurons from the average number of Fos+CTB neurons throughout both groups of animals prior to injection, 154+28, while vehicle injection yielded a 5+0.8% increase from the baseline. This suggests that by inhibiting the CVLM, RVM activation will increase. This finding helps us to better understand the baroreceptor reflex control pathway and how it is mediated.

This study has proven to be very useful for our work at the Mueller lab. We used the Fos+CTB staining technique in the current study that I am working on. Also, this study provided us with a better understanding of the overall baroreceptor reflex control of efferent sympathetic nerve activity.

- Ben Huber