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Vestibular modulation of muscle sympathetic nerve activity by the utricle during sub-perceptual sinusoidal linear acceleration in humans
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Abstracts / Autonomic Neuroscience: Basic and Clinical 192 (2015) 56–141
Background: A neural recruitment strategy exists within the sympathetic nervous system (SNS) of young individuals, whereby elevated sympathetic outflow during reflex-mediated stress is associated with recruitment of latent sub-populations of largeramplitude axons and acute modifications in synaptic delays. Aim: We investigated whether these recruitment patterns persist with healthy aging and coronary artery disease (CAD). Methods: Muscle sympathetic nerve activity (MSNA; microneurography) was measured in 14 young healthy individuals (YH; 25 ± 4 yrs), 14 older healthy individuals (OH; 59 ± 9 yrs), and 15 CAD patients (63 ± 11 yrs) at baseline and during a maximal end-inspiratory apnea. Action potential (AP) patterns were studied using a novel AP analysis technique. Results: Baseline burst frequency was greater in OH (35 ± 10 bursts/min) and CAD (39 ± 5 bursts/min), compared to YH (17 ± 7 bursts/min; all P b 0.001). APs/min and APs/burst increased during apnea (time effect; all P b 0.001). When APs were binned according to peak-to-peak amplitude (i.e., into ‘clusters’), total ‘clusters’ increased during apnea in YH (Δ6 ± 3; P b 0.001) and OH (Δ2 ± 1; P b 0.01), but was unchanged in CAD (Δ0 ± 1; P N 0.05). The number of active clusters/burst increased during apnea in YH (Δ2 ± 1; P b 0.001), OH (Δ1 ± 1; P b 0.01), and CAD (Δ1 ± 1; P = 0.01) groups, although greater change occurred in YH versus OH and CAD (all P b 0.01). In all groups, a pattern emerged where the cluster size-latency profile was shifted downwards for every corresponding cluster during apnea. Conclusion: The capacity of the SNS to recruit latent sub-populations of larger-amplitude axons is reduced with healthy aging and lost in CAD, while the ability to acutely modify synaptic delays appears unaltered. doi:10.1016/j.autneu.2015.07.190
P15.2 Vestibular modulation of muscle sympathetic nerve activity by the utricle during sub-perceptual sinusoidal linear acceleration in humans E. Hammama, C.L.V. Haub, K.S. Wongb, K. Kwokc, V.G. Macefielda,d a School of Medicine, University of Western Sydney, Sydney, Australia b CLP Power Wind/Wave Tunnel Facility, Honk Kong University of Science & Technology, Clear Water Bay, Hong Kong c Institute for Infrastructure Engineering, University of Western Sydney, Sydney, Australia d Neuroscience Research Australia, Sydney, Australia We assessed the capacity for the vestibular utricle to modulate muscle sympathetic nerve activity (MSNA) during sinusoidal linear acceleration at amplitudes extending from imperceptible to clearly perceptible. Subjects (n = 16) were seated in a sealed room, eliminating visual cues, mounted on a linear motor that could deliver peak sinusoidal accelerations of 30 mG in the antero-posterior direction. Subjects sat on a chair with their neck and head supported vertically, thereby minimizing somatosensory cues, facing the direction of motion in the anterior direction. Each block of sinusoidal motion was applied at a time unknown to subjects and in a random order of amplitudes (1.25, 2.5, 5, 10, 20 and 30 mG), at a constant frequency of 0.2 Hz. MSNA was recorded via tungsten microelectrodes inserted into the common peroneal nerve. Subjects used a linear potentiometer aligned to the axis of motion to indicate any perceived movement, which was compared with the accelerometer signal of actual room movement. On average, 67% correct detection of movement did not occur until 6.5 mG, with correct knowledge of the direction of movement at ~10 mG. Cross-correlation analysis revealed potent sinusoidal modulation of MSNA even at accelerations subjects could not perceive (1.25-5 mG). The modulation index showed a positive linear increase with
acceleration amplitude, with the modulation being significantly higher (25.3 ± 3.7 %) at 30 mG than at 1.25 mG (15.5 ± 1.2 %). We conclude that selective activation of the vestibular utricle causes a pronounced modulation of MSNA, even at levels well below perceptual threshold. doi:10.1016/j.autneu.2015.07.191
P15.3 Quantitative analysis of human cutaneous vasomotor innervation E. Sohna, C.H. Gibbonsb, N. Wangb, R. Freemanb a Department of Neurology, Chungnam National University Hospital, Daejeon, South Korea b Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA Background: Skin biopsy is well-established technique for quantifying epidermal sensory nerve fiber density. Several studies have established the utility of the skin biopsy in quantifying the autonomic innervation of arrector pili muscles and sweat glands, however, quantification of the cutaneous vasomotor innervation is methodologically more challenging and has not been systematically studied. These challenges include the diffuse distribution of cutaneous neurovascular system and establishing criteria for innervation of vascular structures. Aim: We conducted this study to address these challenges and establish a reliable method for the assessment of cutaneous vasomotor innervation. Method: Eight healthy controls (mean age, 30.4 ± 6.1; Women/Men = 3) without medical conditions that might cause microcirculation abnormality or neuropathy were studied. Skin biopsy samples were obtained from the distal thigh and the distal leg. Biopsies were cut into 50 μm sections and underwent immunohistochemical staining with the pan-axonal marker PGP 9.5, and with the endothelial marker CD 31. Confocal Z-stack images were used to analyze the whole thickness of the tissues. We used an unbiased stereological method to quantify the dermal neurovascular system. All the nerve fibers, blood vessels, and co-localized nerves and blood vessels within 500 μm from the epidermal surface were counted. These were normalized by the total area. Neural density, vascular density, and neurovascular density were calculated. Inter-rater and intra-rater reliability were performed. Result: Neural densities were 0.22 ± 0.03 at the distal leg and 0.25 ± 0.05 at the distal thigh. Vascular densities were 0.32 ± 0.04 and 0.33 ± 0.04 at corresponding area. Neurovascular densities were 0.13 ± 0.02 and 0.15 ± 0.03 at each site. The Cronbach’s alpha of this method were high (0.92 ~ 0.98). Conclusion: We report the successful application of an unbiased stereological method to quantify the cutaneous neurovascular density. This method is a reliable way to investigate the dermal neurovascular system and define the relationship between the vascular and the vasomotor nervous system. We anticipate that this method will provide greater understanding of the pathogenic mechanisms of disease that affect the peripheral vascular system.
doi:10.1016/j.autneu.2015.07.192
P15.4 Interaction between h-current and nicotinic EPSPs in sympathetic neurons serves to modulate synaptic amplification in ganglia J.P. Horn, K.M. Sikora, K. Clark, M.G. Springer, P.H.M. Kullmann Department of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
Abstracts / Autonomic Neuroscience: Basic and Clinical 192 (2015) 56–141
Background: A neural recruitment strategy exists within the sympathetic nervous system (SNS) of young individuals, whereby elevated sympathetic outflow during reflex-mediated stress is associated with recruitment of latent sub-populations of largeramplitude axons and acute modifications in synaptic delays. Aim: We investigated whether these recruitment patterns persist with healthy aging and coronary artery disease (CAD). Methods: Muscle sympathetic nerve activity (MSNA; microneurography) was measured in 14 young healthy individuals (YH; 25 ± 4 yrs), 14 older healthy individuals (OH; 59 ± 9 yrs), and 15 CAD patients (63 ± 11 yrs) at baseline and during a maximal end-inspiratory apnea. Action potential (AP) patterns were studied using a novel AP analysis technique. Results: Baseline burst frequency was greater in OH (35 ± 10 bursts/min) and CAD (39 ± 5 bursts/min), compared to YH (17 ± 7 bursts/min; all P b 0.001). APs/min and APs/burst increased during apnea (time effect; all P b 0.001). When APs were binned according to peak-to-peak amplitude (i.e., into ‘clusters’), total ‘clusters’ increased during apnea in YH (Δ6 ± 3; P b 0.001) and OH (Δ2 ± 1; P b 0.01), but was unchanged in CAD (Δ0 ± 1; P N 0.05). The number of active clusters/burst increased during apnea in YH (Δ2 ± 1; P b 0.001), OH (Δ1 ± 1; P b 0.01), and CAD (Δ1 ± 1; P = 0.01) groups, although greater change occurred in YH versus OH and CAD (all P b 0.01). In all groups, a pattern emerged where the cluster size-latency profile was shifted downwards for every corresponding cluster during apnea. Conclusion: The capacity of the SNS to recruit latent sub-populations of larger-amplitude axons is reduced with healthy aging and lost in CAD, while the ability to acutely modify synaptic delays appears unaltered. doi:10.1016/j.autneu.2015.07.190
P15.2 Vestibular modulation of muscle sympathetic nerve activity by the utricle during sub-perceptual sinusoidal linear acceleration in humans E. Hammama, C.L.V. Haub, K.S. Wongb, K. Kwokc, V.G. Macefielda,d a School of Medicine, University of Western Sydney, Sydney, Australia b CLP Power Wind/Wave Tunnel Facility, Honk Kong University of Science & Technology, Clear Water Bay, Hong Kong c Institute for Infrastructure Engineering, University of Western Sydney, Sydney, Australia d Neuroscience Research Australia, Sydney, Australia We assessed the capacity for the vestibular utricle to modulate muscle sympathetic nerve activity (MSNA) during sinusoidal linear acceleration at amplitudes extending from imperceptible to clearly perceptible. Subjects (n = 16) were seated in a sealed room, eliminating visual cues, mounted on a linear motor that could deliver peak sinusoidal accelerations of 30 mG in the antero-posterior direction. Subjects sat on a chair with their neck and head supported vertically, thereby minimizing somatosensory cues, facing the direction of motion in the anterior direction. Each block of sinusoidal motion was applied at a time unknown to subjects and in a random order of amplitudes (1.25, 2.5, 5, 10, 20 and 30 mG), at a constant frequency of 0.2 Hz. MSNA was recorded via tungsten microelectrodes inserted into the common peroneal nerve. Subjects used a linear potentiometer aligned to the axis of motion to indicate any perceived movement, which was compared with the accelerometer signal of actual room movement. On average, 67% correct detection of movement did not occur until 6.5 mG, with correct knowledge of the direction of movement at ~10 mG. Cross-correlation analysis revealed potent sinusoidal modulation of MSNA even at accelerations subjects could not perceive (1.25-5 mG). The modulation index showed a positive linear increase with
acceleration amplitude, with the modulation being significantly higher (25.3 ± 3.7 %) at 30 mG than at 1.25 mG (15.5 ± 1.2 %). We conclude that selective activation of the vestibular utricle causes a pronounced modulation of MSNA, even at levels well below perceptual threshold. doi:10.1016/j.autneu.2015.07.191
P15.3 Quantitative analysis of human cutaneous vasomotor innervation E. Sohna, C.H. Gibbonsb, N. Wangb, R. Freemanb a Department of Neurology, Chungnam National University Hospital, Daejeon, South Korea b Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA Background: Skin biopsy is well-established technique for quantifying epidermal sensory nerve fiber density. Several studies have established the utility of the skin biopsy in quantifying the autonomic innervation of arrector pili muscles and sweat glands, however, quantification of the cutaneous vasomotor innervation is methodologically more challenging and has not been systematically studied. These challenges include the diffuse distribution of cutaneous neurovascular system and establishing criteria for innervation of vascular structures. Aim: We conducted this study to address these challenges and establish a reliable method for the assessment of cutaneous vasomotor innervation. Method: Eight healthy controls (mean age, 30.4 ± 6.1; Women/Men = 3) without medical conditions that might cause microcirculation abnormality or neuropathy were studied. Skin biopsy samples were obtained from the distal thigh and the distal leg. Biopsies were cut into 50 μm sections and underwent immunohistochemical staining with the pan-axonal marker PGP 9.5, and with the endothelial marker CD 31. Confocal Z-stack images were used to analyze the whole thickness of the tissues. We used an unbiased stereological method to quantify the dermal neurovascular system. All the nerve fibers, blood vessels, and co-localized nerves and blood vessels within 500 μm from the epidermal surface were counted. These were normalized by the total area. Neural density, vascular density, and neurovascular density were calculated. Inter-rater and intra-rater reliability were performed. Result: Neural densities were 0.22 ± 0.03 at the distal leg and 0.25 ± 0.05 at the distal thigh. Vascular densities were 0.32 ± 0.04 and 0.33 ± 0.04 at corresponding area. Neurovascular densities were 0.13 ± 0.02 and 0.15 ± 0.03 at each site. The Cronbach’s alpha of this method were high (0.92 ~ 0.98). Conclusion: We report the successful application of an unbiased stereological method to quantify the cutaneous neurovascular density. This method is a reliable way to investigate the dermal neurovascular system and define the relationship between the vascular and the vasomotor nervous system. We anticipate that this method will provide greater understanding of the pathogenic mechanisms of disease that affect the peripheral vascular system.
doi:10.1016/j.autneu.2015.07.192
P15.4 Interaction between h-current and nicotinic EPSPs in sympathetic neurons serves to modulate synaptic amplification in ganglia J.P. Horn, K.M. Sikora, K. Clark, M.G. Springer, P.H.M. Kullmann Department of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA