Influence of Vagotomy on Monosynaptic Transmission at Second-Order Nucleus Tractus Solitarius Synapses

Abstract

Swartz JB, Weinreich D. Influence of vagotomy on monosynaptic transmission at second-order nucleus tractus solitarius synapses. J Neurophysiol 102: 2846 -2855, 2009. First published September 2, 2009 doi:10.1152/jn.00168.2009. Manipulations of vagal activity are used to treat medical pathologies, but the underlying CNS changes caused by these treatments are not well understood. Furthermore, heart and lung transplant as well as treatments for many gastrointestinal disorders result in section of the vagus nerve (vagotomy). Following unilateral vagotomy under isoflurane anesthesia of SpragueDawley rats, electrophysiological properties were recorded with whole cell patch techniques in horizontal brain stem slices. Vagotomy significantly reduced the median amplitude of evoked excitatory postsynaptic currents (evEPSCs; -121; n ϭ 43) in the nucleus tractus solitarius (NTS) when compared with controls (-157 pA; n ϭ 66; P Ͻ 0.05) but had no significant effect on the passive properties or on the average amplitude or frequency of miniature EPSCs. The degree of synaptic failure exhibited during a 50-Hz train of stimuli was used to define two separate classes of synapses: "low failure" and "high failure" (HF); failure rates Ͻ5 and Ն5%, respectively. HF synapses had significantly smaller median evEPSCs (-88 vs. -184 pA; P Ͻ 0.05). After vagotomy, the percentage of HF synapses nearly doubled to 56% (n ϭ 24/43) when compared with controls (30%; n ϭ 20/66). Additionally, the overall percentage of failures after the second to fifth stimuli significantly increased by at least twofold. These results suggest that vagotomy causes a decrease in synaptic efficacy by both increasing the overall percentage of synaptic failures and shifting the population of NTS synapses toward more HF transmission. In addition, the alterations due to vagotomy are likely to be presynaptic in nature. I N T R O D U C T I O NThe nucleus tractus solitarius (NTS), located in the brain stem, is critical to the receipt, integration, and transmission of primary sensory signals coming from visceral organs (Loewy 1990). These sensory signals, coded in the pattern of action potential activity, are sent to the NTS via axons of the vagus nerve where they are subsequently translated and processed by NTS synapses. Thus second-order NTS neurons do not merely relay vagal activity to higher brain centers. Instead they incorporate afferent information with activity in local circuits and upstream efferent signals to control autonomic homeostasis, the maintenance of equilibrium between the sympathetic and parasympathetic systems (Andresen and Kunze 1994;Bonham et al. 2006;Travagli et al. 2006). Consequently, alterations to the information coming from vagal afferents could change synaptic communication to NTS neurons, modifying upstream circuits and throwing off autonomic homeostatic balance.There are many serious disorders, such as asthma and hypertension, that can alter the excitability of peripheral nerve terminals of the vagus nerve. Several studies have revealed that ana...

Withdrawal and restoration of central vagal afferents within the dorsal vagal complex following subdiaphragmatic vagotomy

“…Our results show that the number of synapses within the NTS at 60 days post vagotomy did not significantly differ from controls, suggesting that central vagal synaptic connections were largely restored. Previous results suggest that unilateral cervical vagotomy causes a decrease in synaptic efficacy by both increasing the overall percentage of synaptic failures and shifting the population of NTS synapses toward a more high failure transmission (Swartz and Weinreich, ). This study combined recordings from across animals 6–30 days post vagotomy, a time period we now appreciate exhibits dynamic changes in afferent death and synaptic withdrawal/reinnervation.…”

“…Our results are consistent with this report in that synaptic strength is diminished primarily via a decrease in a presynaptic release probability although we did not observe the dramatic increase in failures. This was likely because we unintentionally masked this effect by increasing the release probability through recording in a 2‐mM bath calcium, whereas Swartz and Weinreich () recorded in a 1‐mM bath calcium. Furthermore, our lesion targeted the subdiaphragmatic abdominal afferents, which provide a dominant innervation into the medial NTS, resulting in a somewhat less “traumatic” injury.…”

“…Changes in the number of synapses in the spinal cord (Brannstrom and Kellerth, ; White and Kocsis, ; Sun et al, ) and the hindbrain (Gallaher et al, ) following damage to their peripheral axons suggest that central afferents reorganize their synaptic connections with the second‐order neurons after injury. Electrophysiological recordings of vagal afferent to the NTS synapses following complete unilateral cervical vagotomy demonstrated a decrease in synaptic efficacy, an effect mediated via failure to translate presynaptic action‐potential invasion to vesicular glutamate release (Swartz and Weinreich, ). Although this finding provides functional evidence of synaptic reorganization, the extent of axonal regeneration/reinnervation over longer periods of time was not determined.…”

Mechanisms of Dyspnea

“…Signal processing at synapses in the NTS, which incorporates activity in local circuits and upstream efferent signals, determines the output of sensory information from the lungs and airways to all downstream synapses in the refl ex pathways, including higher brain regions. 38,39 Anatomic afferent input from the NTS to the thalamus has been documented in rats, 40 and in monkeys the thalamus is activated by vagus nerve afferents. 41 In cats and rats, stimulation of the cervical vagus nerves results in activation of the somatosensory cortex 42 and insular cortex.…”

Exercise training to reduce sympathetic nerve activity in heart failure patients. A systematic review and meta-analysis

“… 8 The pathophysiology is characterized by an imbalance in the autonomic control of the cardiovascular system, with a predominance of sympathetic nervous systems and inhibition of parasympathetic nervous systems. 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 This imbalance promotes the activation of renin–angiotensin system and mechanisms associated with myocardial remodeling, which worse the disease prognosis and increases patient mortality rates. 11 , 12 , 13 , 14 …”