Role of ventrolateral medulla in generating the 10-Hz rhythm in sympathetic nerve discharge

Abstract

We recorded changes in right inferior cardiac and either left inferior cardiac or left vertebral sympathetic nerve discharge (SND) produced by unilateral microinjections of GABA-A and excitatory amino acid (EAA) receptor antagonists into the ventrolateral medulla (VLM) of urethane-anesthetized, baroreceptor-denervated cats. Unilateral microinjections of GABA-A receptor antagonists, SR-95531 or bicuculline, into single tracks in VLM anywhere between 1 and 5 mm rostral to the obex eliminated or markedly reduced 10-Hz power in SND on both sides of the body. Low-frequency components (<6 Hz) of SND were unaffected. Complete blockade of the 10-Hz rhythm occurred with a dose of SR-95531 as low as 6.25 pmol in a 50-nl volume. Unilateral microinjections of the nonselective EAA receptor antagonist, kynurenate (KYN; 7.5 nmol), into the caudal or rostral VLM significantly reduced, but did not eliminate, 10-Hz SND ipsilateral to the injection sites, while 10-Hz SND contralateral to the injection sites was not significantly changed. These observations suggest that 1) GABAergic transmission in VLM is critical for generation of the 10-Hz rhythm, 2) the caudal and rostral portions of VLM act together to generate the 10-Hz rhythm, and 3) 10-Hz rhythm generation depends, at least in part, on tonic or phasic excitatory drive to GABAergic interneurons in caudal VLM and presympathetic neurons in rostral VLM. The data also suggest that pathways interconnecting the two halves of the brain stem play an important role in promoting 10-Hz rhythm generation.

What can we learn about neural control of the cardiovascular system by studying rhythms in sympathetic nerve activity?

“…With this approach, one can quantify the average duration of integrated epoch or the slope of the integrated signal. In this example, the amount of SNA markedly decreased as sequential injections of a GABA-A receptor antagonist (upward tick marks in the trace below SNA) were made into the caudal ventrolateral medulla (CVLM) of a urethane-anesthetized cat (Barman and Gebber, 2007). …”

“…Although most recognized for having cardiac-related and respiratory-related discharges, sympathetic neural networks are quite complex and generate a variety of periodicities that range between ~0.04 and 10 Hz or even higher, and even diurnal variations, depending on the physiological or pathophysiological conditions, type of nerve being analyzed, age of the subject, and the species (Barman and Gebber, 2000; Barman and Kenney, 2007; Chang et al, 1999; Charkoudian and Wallin, 2014; Hashimoto et al, 1999; Malpas, 1998, 2010; Narkiewicz et al, 2002). …”

Role of serotonergic input to the ventrolateral medulla in expression of the 10-Hz sympathetic nerve rhythm

“…Potentials were recorded monophasically from the central ends of the cut nerves placed on platinum bipolar electrodes. The capacitycoupled preamplifier band pass was set at 1-1,000 Hz so that the synchronized discharges of sympathetic fibers appeared as slow waves (4,5,7,24).…”

“…Third, chemical inactivation of the rostral VLM, caudal VLM, or medullary raphé with microinjection of muscimol reduces or eliminates 10-Hz SND (10,39). Barman and Gebber (7) reported that unilateral microinjections of as little as 6.25 pmol of the selective GABA-A receptor antagonist SR-95531 into the VLM at any level between 1 and 5 mm rostral to the obex eliminated 10-Hz SND. This led Barman and Gebber (7) to propose that 1) GABAergic transmission in the VLM is critical for generation of the 10-Hz rhythm, and 2) neurons in caudal and rostral portions of the VLM act in combination to help generate the 10-Hz rhythm in SND.…”

Sex, the brain and hypertension: brain oestrogen receptors and high blood pressure risk factors

“…In both human and animal studies, increases in RVLM activity are known to be associated with SNA and SNA-related changes in BP [39][40][41][42][43]. The RVLM expresses both ERα and ERβ receptors [44], and activation of these receptors via direct injection of oestrogen into the RVLM results in a decrease in SNA [45].…”