Dynamic clamp analysis of synaptic integration in sympathetic ganglia

Horn, John P.; Kullmann, Paul H. M.

doi:10.1007/s11062-008-9002-y

Cited by 8 publications

(8 citation statements)

References 40 publications

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“…While earlier studies in animals may provide some insight to the mechanisms (e.g. ganglionic convergence) contributing to the present observations, the focus on compound APs or single‐unit recordings in these investigations (Obrador & Odoriz, ; Karila & Horn, ; Horn & Kullmann, ; Bratton et al . ; Rimmer & Horn, ; Springer et al .…”

Section: Discussionmentioning

confidence: 90%

The role of the paravertebral ganglia in human sympathetic neural discharge patterns

Klassen

Limberg

Baker

et al. 2018

The Journal of Physiology

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Do the ganglia contribute to the ordered behaviour of postganglionic neuronal discharge within the sympathetic nervous system? To further understand the functional organization of the sympathetic nervous system we employed the microneurographic approach to record muscle sympathetic nerve activity (MSNA) and a continuous wavelet transform to study postganglionic action potential (AP) behaviour during nicotinic blockade at the ganglia (trimethaphan camsylate, 1-7 mg min ) in seven females (37 ± 5 years). Trimethaphan elicited a progressive reduction in sympathetic outflow characterized by fewer integrated bursts with decaying amplitude. Underlying trimethaphan-mediated attenuations in integrated MSNA were reductions in AP incidence (186 ± 101 to 29 ± 31 AP (100 beats) ) and AP content per integrated burst (7 ± 2 to 3 ± 1 APs burst ) (both P < 0.01) in the final minute of detectable bursting activity in the trimethaphan condition, compared to baseline. We observed an ordered de-recruitment of larger to smaller AP clusters active at baseline (14 ± 3 to 8 ± 2 active AP clusters, P < 0.01). Following cessation of integrated bursts in the trimethaphan condition, the smallest 6 ± 2 sympathetic AP clusters persisted to fire in an asynchronous pattern (49 ± 41 AP (100 beats) ) in all participants. Valsalva's manoeuvre did not increase the incidence of these persistent APs (60 ± 42 AP (100 beats) , P = 0.52), or recruit any larger APs in six of seven participants (6 ± 1 total AP clusters, P = 0.30). These data suggest that the ganglia participate in the ordered recruitment of differently sized postganglionic sympathetic nerves.

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Section: Discussionmentioning

confidence: 90%

The role of the paravertebral ganglia in human sympathetic neural discharge patterns

Klassen

Limberg

Baker

et al. 2018

The Journal of Physiology

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“…The ganglia are proposed to exhibit the ability to amplify the preganglionic signal by distributing axons that produce suprathreshold (i.e., "strong") excitatory postsynaptic potentials from one preganglionic to multiple (e.g., 2-15) postganglionic neurons (Bahr et al 1986;Jänig and Häbler 2000;McLachlan 2003;Purves et al 1986;Wang et al 1995). Furthermore, computational and advanced dynamic clamping methods (Horn and Kullmann 2007;Rimmer and Horn 2010;Springer et al 2015) suggest the ability to enhance the firing probabilities of any postganglionic neuron through convergent synapses from multiple preganglionic neurons that individually produce subthreshold excitatory postsynaptic potentials but, depending on their timing, could summate to cause a postganglionic discharge. How these concepts apply to different ganglia or postganglionic axons of varying size and/or varying targets, or in human ganglia, remain to be studied.…”

Section: The Validity and Reliability Of Postganglionic Sna To Reflecmentioning

confidence: 99%

“…While measuring integrated burst latency changes as a function of burst size, Wallin and colleagues (Wallin et al 1994) wondered about the possibility of modifiable synaptic latencies but no mechanisms have been explored. One possible determinant of these observations may include variations in the number and impact of converging primary and secondary synapses with postganglionic neurons (Bratton et al 2010;Horn and Kullmann 2007;Schobesberger et al 2000) that could affect the timing of postganglionic AP generation. Finally, the relevance of such latency changes remains unknown either from their central generation or in terms of potential variations in end organ control.…”

Section: )mentioning

confidence: 99%

Fifty years of microneurography: learning the language of the peripheral sympathetic nervous system in humans

Shoemaker

Klassen

Badrov

et al. 2018

Journal of Neurophysiology

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As a primary component of homeostasis, the sympathetic nervous system enables rapid adjustments to stress through its ability to communicate messages among organs and cause targeted and graded end organ responses. Key in this communication model is the pattern of neural signals emanating from the central to peripheral components of the sympathetic nervous system. But what is the communication strategy employed in peripheral sympathetic nerve activity (SNA)? Can we develop and interpret the system of coding in SNA that improves our understanding of the neural control of the circulation? In 1968, Hagbarth and Vallbo (Hagbarth KE, Vallbo AB. Acta Physiol Scand 74: 96-108, 1968) reported the first use of microneurographic methods to record sympathetic discharges in peripheral nerves of conscious humans, allowing quantification of SNA at rest and sympathetic responsiveness to physiological stressors in health and disease. This technique also has enabled a growing investigation into the coding patterns within, and cardiovascular outcomes associated with, postganglionic SNA. This review outlines how results obtained by microneurographic means have improved our understanding of SNA outflow patterns at the action potential level, focusing on SNA directed toward skeletal muscle in conscious humans.

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“…Sympathetic neurons in paravertebral ganglia typically receive one strong nicotinic input that always triggers an action potential. We have proposed that the strength and convergence of weaker subthreshold inputs can result in additional action potentials and thereby generate gain by amplifying preganglionic activity (Karila & Horn, ; Horn & Kullmann, ). The gain hypothesis rests on the idea that summation between pairs of subthreshold EPSPs is sufficient to initiate action potentials in ganglion cells.…”

Section: Introductionmentioning

confidence: 99%

Virtual leak channels modulate firing dynamics and synaptic integration in rat sympathetic neurons: implications for ganglionic transmission in vivo

Springer

Kullmann

Horn

2014

The Journal of Physiology

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Key pointsr The synaptic organization of paravertebral sympathetic ganglia enables them to relay activity from the spinal cord to the periphery and thereby control autonomic functions, including blood pressure and body temperature.r The present experiments were done to reconcile conflicting observations in tissue culture, intact isolated ganglia and living animals. By recording intracellularly from dissociated neurons and intact ganglia, we found that when electrode damage makes cells leaky it could profoundly distort cellular excitability and the integration of synaptic potentials.r The experiments relied on the dynamic clamp method, which allows the creation of virtual ion channels by injecting current into a cell based upon a mathematical model and using rapid feedback between the model and cell.r The results support the hypothesis that sympathetic ganglia can produce a 2.4-fold amplification of presynaptic activity. This could aid understanding of the neural hyperactivity that is believed to drive high blood pressure in some patients. AbstractThe excitability of rat sympathetic neurons and integration of nicotinic EPSPs were compared in primary cell culture and in the acutely isolated intact superior cervical ganglion using whole cell patch electrode recordings. When repetitive firing was classified by Hodgkin's criteria in cultured cells, 18% displayed tonic class 1 excitability, 36% displayed adapting class 2 excitability and 46% displayed phasic class 3 excitability. In the intact ganglion, 71% of cells were class 1 and 29% were class 2. This diverges from microelectrode reports that nearly 100% of superior cervical ganglion neurons show phasic class 3 firing. The hypothesis that the disparity between patch and microelectrode data arises from a shunt conductance was tested using the dynamic clamp in cell culture. Non-depolarizing shunts of 3-10 nS converted cells from classes 1 and 2 to class 3 dynamics with current-voltage relations that replicated microelectrode data. Primary and secondary EPSPs recorded from the intact superior cervical ganglion were modelled as virtual synapses in cell culture using the dynamic clamp. Stimulating sympathetic neurons with virtual synaptic activity, designed to replicate in vivo recordings of EPSPs in muscle vasoconstrictor neurons, produced a 2.4-fold amplification of presynaptic activity. This gain in postsynaptic output did not differ between neurons displaying the three classes of excitability. Mimicry of microelectrode damage by virtual leak channels reduced and eventually obliterated synaptic gain by inhibiting summation of subthreshold EPSPs. These results provide a framework for interpreting sympathetic activity recorded from intact animals and support the hypothesis that paravertebral ganglia function as activity-dependent amplifiers of spinal output from preganglionic circuitry.

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Dynamic clamp analysis of synaptic integration in sympathetic ganglia

Cited by 8 publications

References 40 publications

The role of the paravertebral ganglia in human sympathetic neural discharge patterns

The role of the paravertebral ganglia in human sympathetic neural discharge patterns

Fifty years of microneurography: learning the language of the peripheral sympathetic nervous system in humans

Virtual leak channels modulate firing dynamics and synaptic integration in rat sympathetic neurons: implications for ganglionic transmission in vivo

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