Vagus nerve stimulation activates nucleus of solitary tract neurons via supramedullary pathways. (17th November 2021)

• Record Type: Journal Article
• Authors: Cooper, Coty M.; Farrand, Ariana Q.; Andresen, Michael C.; Beaumont, Eric
• Is Part Of: Journal of physiology. Volume 599:Number 23(2021)
• Page Start: 5261
• Page End: 5279
• Publication Date: 2021-11-17
• Subjects: in vivo electrophysiology -- nucleus of the solitary tract -- rats -- vagal primary afferents -- vagus nerve stimulation; Physiology -- Periodicals; 612.005
• DOI: 10.1113/JP282064
• Languages: English
• ISSNs: 0022-3751

Abstract

Abstract : Abstract: Vagus nerve stimulation (VNS) treats patients with drug‐resistant epilepsy, depression and heart failure, but the mechanisms responsible are uncertain. The mild stimulus intensities used in chronic VNS suggest activation of myelinated primary visceral afferents projecting to the nucleus of the solitary tract (NTS). Here, we monitored the activity of second and higher order NTS neurons in response to peripheral vagal activation using therapeutic VNS criteria. A bipolar stimulating electrode activated the left cervical vagus nerve, and stereotaxically placed single tungsten electrodes recorded unit activity from the left caudomedial NTS of chloralose‐anaesthetized rats. High‐intensity single electrical stimuli established vagal afferent conduction velocity (myelinated A‐type or unmyelinated C‐type) as well as synaptic order (second vs . higher order using paired electrical stimuli) for inputs to single NTS neurons. Then, VNS treatment was applied. A mid‐collicular knife cut (KC) divided the brainstem from all supramedullary regions to determine their contribution to NTS activity. Our chief findings indicate that the KC reduced basal spontaneous activity of second‐order NTS neurons receiving myelinated vagal input by 85%. In these neurons, acute VNS increased activity similarly in Control and KC animals. Interestingly, the KC interrupted VNS activation of higher order NTS neurons and second‐order NTS neurons receiving unmyelinated vagal input, indicating that supramedullary descending projections to NTS are needed to amplify the peripheral neuronal signal from VNS. The present study begins to define the pathways activated during VNS and will help to better identify the central nervous system contributions to the therapeutic benefits of VNS therapy. Key points: Vagus nerve stimulation is routinely used in the clinic to treat epilepsy and depression, despite our uncertainty about how this treatment works. For this study, the connections between the nucleus of the solitary tract (NTS) and the higher brain regions were severed to learn more about their contribution to activity of these neurons during stimulation. Severing these brain connections reduced baseline activity as well as reducing stimulation‐induced activation for NTS neurons receiving myelinated vagal input. Higher brain regions play a significant role in maintaining both normal activity in NTS and indirect mechanisms of enhancing NTS neuronal activity during vagus nerve stimulation. Abstract : Abstract figure legend . Mid‐collicular knife cuts (KC) separated the brainstem from the forebrain and resulted in greatly reduced NTS activity as well as VNS responses. (1) NTS neurons receiving vagal A‐fibre Mono input had a spontaneous baseline activity of ∼10 Hz and showed great responses during VNS (left). Following the KC procedure (centre), baseline activity was nearly eliminated and VNS responses slightly decreased (right). (2) A proportion of NTS neurons (∼15%) receiving vagal C‐fibre mono input showed increased activity during VNS identified as Responders (left), which was eliminated after the KC (right). (3) The majority of NTS neurons (∼60%) polysynaptically innervated from the vagus (Poly) showed increased activity during VNS (Responders) (left), which was also eliminated after the KC (right).