Sympathetic nerve activity has more character than you may think

In 1932, Adrian and colleagues published the first recordings of sympathetic nerve activity (SNA) in anaesthetized mammals (cats and rabbits). They reported that the discharges appeared as waves that varied in size and which were often synchronized with both the cardiac and respiratory cycles (Adrian et al. 1932). Since this landmark study, these characteristics of SNA have been documented over and over again by many investigators using a wide range of mammalian species. As described in a delightful historical perspective (Vallbo et al. 2004), 36 years after those first recordings of SNA in animals, Karl-Erik Hagbarth introduced the use of microneurography to record nerve activity in humans by inserting a needle into his own ulnar nerve. This daring early study set the stage for what now seems to be ‘dogma’: the hallmark of SNA traffic to the vasculature of skeletal muscle (MSNA) in resting humans is the appearance of pulse-synchronous bursts of various amplitudes that occur sporadically or in short sequences, often on the time scale of respiration. There is another rather rigid criterion, i.e. that the interval between the preceding R-wave of an electrocardiogram and the peak of each burst must be ∼1.3 s. This is based on the theory that bursts in MSNA occur simply because they are inhibited during systole and released from the inhibition during diastole, as a result of alterations in baroreceptor nerve activity. When recording from sympathetic nerves in animals, one is able to isolate directly the nerve of interest (to just about any target organ) and study its discharge pattern at rest and during various manipulations. As reviewed by Barman & Gebber (2000), this has led to the conclusion that the pattern of SNA can change, depending on the experimental condition (type of anaesthetic used, integrity of the baroreceptor reflex, integrity of supra-spinal structures, etc.). For example, in urethane-anaesthetized or unanaesthetized decerebrate cats, the pattern of SNA can change from a prominent cardiac-related rhythm when arterial pressure is relatively high, to a prominent 10 Hz rhythm when arterial pressure is lowered (i.e. when the activity in baroreceptor afferent nerves is reduced). Substantial data have amassed from studies primarily using anaesthetized cats to support the contention that the brainstem contains the neural circuitry to produce rhythmic discharges of various frequency ranges in sympathetic nerves. These rhythms can be entrained to inputs such as the baroreceptor afferents, lung inflation afferents, and the central respiratory network which gives rise to their characteristic rhythmic pattern (Barman & Gebber, 2000; Barman & Kenney, 2007). When recording from sympathetic nerves in human subjects, one must probe to find an appropriate site (Vallbo et al. 2004), which is defined as a recording that has characteristic pulse-synchronous bursts of activity. So what would happen if an individual had an atypical activity pattern? The investigator might be left to mistakenly conclude that he/she was unsuccessful in recording MSNA. Few investigators seem to challenge the notion that MSNA must have a cardiac-related periodicity. An article by Fagius et al. (1985) is one of a few to report a break from this pattern. They noted that after local anaesthetic blockade of the glossopharyngeal and vagus nerves in the necks of two individuals (baroreceptor deafferentation), the cardiac rhythmicity in MSNA disappeared, and was replaced by a slow, irregular oscillation. The authors speculated that, as in the cat, rhythmicity in MSNA does not simply occur because of the waxing and waning of baroreceptor nerve activity. In this issue of The Journal of Physiology, Cooke et al. (2009) have presented some exquisite examples of changes in the pattern of MSNA in healthy individuals subjected to intense levels of lower body negative pressure (LBNP) to the point of presyncope. This study is the first to accomplish the difficult feat of maintaining stable, high-quality nerve recordings even at chamber pressures of −90 mmHg in some individuals. Amongst their several interesting and novel observations, they have shown that in 10 of 17 individuals, reductions in venous return due to intense LBNP disrupted the typical pulse-synchronous burst pattern of MSNA. Instead, MSNA showed wide burst durations (spanning multiple cardiac cycles), a pattern they refer to as ‘fusing of integrated sympathetic bursts.’ Although they acknowledge that the 0.1 s time constant used to integrate MSNA may contribute to the appearance of the fused slow waves, they also provide evidence that these fused bursts are not likely artifacts of the recording method. Rather, they may reflect a physiological change in the generation of MSNA bursts. These waveforms cannot be described as simple consequences of the baroreceptor reflex, but might reflect a central rhythm-generating process. Does it matter whether bursts in MSNA are merely sculpted by the baroreceptor reflex or are driven by an inherent central rhythm-generating mechanism? Certainly, the existence of the latter implies a more complicated central sympathetic network, allowing the network to function independent of the baroreceptor reflex. This consideration also raises the question of the importance of oscillations or rhythms in nerve signals. Barman & Kenney (2007) present evidence suggesting that rhythmic activity may have several advantages over randomly occurring activity. Rhythmic activity may lead to more effective activation of sympathetic neurons than randomly occurring activity. Also, rhythmicity is important in coordinating activity in different sympathetic nerves, and it may help maintain homeostasis. Cooke et al. (2009) have presented some remarkable findings which indicate that we still have a lot to learn about factors that contribute to the character of MSNA. Future studies may use other manipulations to alter the pattern of MSNA and reveal new features of human autonomic regulatory control processes.