scholarly journals Excitatory Muscarinic Modulation Strengthens Virtual Nicotinic Synapses on Sympathetic Neurons and Thereby Enhances Synaptic Gain

2006 ◽  
Vol 96 (6) ◽  
pp. 3104-3113 ◽  
Author(s):  
Paul H. M. Kullmann ◽  
John P. Horn
Keyword(s):  
Sympathetic Neurons ◽  
Sympathetic Ganglia ◽  
Dynamic Clamp ◽  
Neuronal Types ◽  
Synaptic Gain ◽  
Nicotinic Synapses ◽  
M1 Muscarinic ◽  
The Impact ◽  
Muscarinic Modulation ◽  
M1 Muscarinic Receptors

Acetylcholine excites many neuronal types by binding to postsynaptic m1-muscarinic receptors that signal to ion channels through the Gq/11 protein. To investigate the functional significance of this metabotropic pathway in sympathetic ganglia, we studied how muscarinic excitation modulated the integration of virtual nicotinic excitatory postsynaptic potentials (EPSPs) created in dissociated bullfrog B-type sympathetic neurons with the dynamic-clamp technique. Muscarine (1 μM) strengthened the impact of virtual synapses by reducing the artificial nicotinic conductance required to reach the postsynaptic firing threshold from 20.9 ± 5.4 to 13.1 ± 3.1 nS. Consequently, postganglionic action potential output increased by 4–215% when driven by different patterns of virtual presynaptic activity that were chosen to reflect the range of physiological firing rates and convergence levels seen in amphibian and mammalian sympathetic ganglia. In addition to inhibiting the M-type K+ conductance, muscarine activated a leak conductance in three of 37 cells. When this leak conductance was reproduced with the dynamic clamp, it also acted to strengthen virtual nicotinic synapses and enhance postganglionic spike output. Combining pharmacological M-conductance suppression with virtual leak activation, at resting potentials between −50 and −55 mV, produced synergistic strengthening of nicotinic synapses and an increase in the integrated postganglionic spike output. Together, these results reveal how muscarinic activation of a branched metabotropic pathway can enhance integration of fast EPSPs by modulating their effective strength. The results also support the hypothesis that muscarinic synapses permit faster and more accurate feedback control of autonomic behaviors by generating gain through synaptic amplification in sympathetic ganglia.

Estimating Use-Dependent Synaptic Gain in Autonomic Ganglia by Computational Simulation and Dynamic-Clamp Analysis

2004 ◽  
Vol 92 (5) ◽  
pp. 2659-2671 ◽  
Author(s):  
Diek W. Wheeler ◽  
Paul H. M. Kullmann ◽  
John P. Horn
Keyword(s):  
Sympathetic Neurons ◽  
Computational Simulation ◽  
Sympathetic Neuron ◽  
Sympathetic Ganglia ◽  
Spike Timing ◽  
Calcium Currents ◽  
Dynamic Clamp ◽  
Autonomic Ganglia ◽  
Postsynaptic Spike ◽  
Synaptic Gain

Biological gain mechanisms regulate the sensitivity and dynamics of signaling pathways at the systemic, cellular, and molecular levels. In the sympathetic nervous system, gain in sensory-motor feedback loops is essential for homeostatic regulation of blood pressure and body temperature. This study shows how synaptic convergence and plasticity can interact to generate synaptic gain in autonomic ganglia and thereby enhance homeostatic control. Using a conductance-based computational model of an idealized sympathetic neuron, we simulated the postganglionic response to noisy patterns of presynaptic activity and found that a threefold amplification in postsynaptic spike output can arise in ganglia, depending on the number and strength of nicotinic synapses, the presynaptic firing rate, the extent of presynaptic facilitation, and the expression of muscarinic and peptidergic excitation. The simulations also showed that postsynaptic refractory periods serve to limit synaptic gain and alter postsynaptic spike timing. Synaptic gain was measured by stimulating dissociated bullfrog sympathetic neurons with 1–10 virtual synapses using a dynamic clamp. As in simulations, the threshold synaptic conductance for nicotinic excitation of firing was typically 10–15 nS, and synaptic gain increased with higher levels of nicotinic convergence. Unlike the model, gain in neurons sometimes declined during stimulation. This postsynaptic effect was partially blocked by 10 μM Cd2+, which inhibits voltage-dependent calcium currents. These results support a general model in which the circuit variations observed in parasympathetic and sympathetic ganglia, as well as other neural relays, can enable functional subsets of neurons to behave either as 1:1 relays, variable amplifiers, or switches.

scholarly journals Excitation of rat sympathetic neurons via M1 muscarinic receptors independently of Kv7 channels

2014 ◽  
Vol 466 (12) ◽  
pp. 2289-2303 ◽  
Author(s):  
Isabella Salzer ◽  
Hend Gafar ◽  
Viola Gindl ◽  
Peter Mahlknecht ◽  
Helmut Drobny ◽  
...  
Keyword(s):  
Muscarinic Receptors ◽  
Sympathetic Neurons ◽  
Kv7 Channels ◽  
M1 Muscarinic ◽  
M1 Muscarinic Receptors

scholarly journals Converging preganglionic axons refine without synaptic transmission when targets downstream of sympathetic nerves are active

2020 ◽  
Author(s):  
Yumaine Chong ◽  
Ellis Cooper
Keyword(s):  
Synaptic Transmission ◽  
Single Cell ◽  
Sympathetic Neurons ◽  
Sympathetic Nerves ◽  
Sympathetic Ganglia ◽  
Synaptic Activity ◽  
Postsynaptic Activity ◽  
Single Cell Rna Sequencing ◽  
The Impact ◽  
Target Activity

AbstractIt is well accepted that refinement of converging presynaptic inputs depends on postsynaptic activity; however, it remains unclear how this developmental event is initiated. To address this, we developed a mosaic model where synaptically-active and synaptically-inactive sympathetic neurons develop side-by-side in the same ganglion. Surprisingly, we show that converging presynaptic inputs refine on neurons even without synaptic transmission as long as the synaptically-silent neurons share targets with synaptically-active neurons. In addition, our single-cell RNA sequencing experiments show that sympathetic ganglia contain at least 7 neuronal subtypes that decode the impact of synaptic activity differently, including their ability to maintain an adrenergic phenotype. Our results provide a new view on the roles that synaptic transmission and retrograde target activity have on developing circuits.

scholarly journals HCN hyperpolarization-activated cation channels strengthen virtual nicotinic EPSPs and thereby elevate synaptic amplification in rat sympathetic neurons

2016 ◽  
Vol 116 (2) ◽  
pp. 438-447 ◽  
Author(s):  
Paul H. M. Kullmann ◽  
Kristine M. Sikora ◽  
K. Lyles Clark ◽  
Irene Arduini ◽  
Mitchell G. Springer ◽  
...  
Keyword(s):  
Voltage Clamp ◽  
Cyclic Nucleotide ◽  
Sympathetic Neurons ◽  
Reversal Potential ◽  
Hcn Channels ◽  
Dynamic Clamp ◽  
Messenger Rnas ◽  
Cation Conductance ◽  
Cervical Ganglion ◽  
Synaptic Gain

The influence of hyperpolarization-activated cation current (h-current; Ih) upon synaptic integration in paravertebral sympathetic neurons was studied together with expression of hyperpolarization-activated cyclic nucleotide-gated (HCN) subunit isoforms. All four HCN subunits were detected in homogenates of the rat superior cervical ganglion (SCG) using the PCR to amplify reverse-transcribed messenger RNAs (RT-PCR) and using quantitative PCR. Voltage clamp recordings from dissociated SCG neurons at 35°C detected Ih in all cells, with a maximum hyperpolarization-activated cation conductance of 1.2 ± 0.1 nS, half-maximal activation at −87.6 mV, and reversal potential of −31.6 mV. Interaction between Ih and synaptic potentials was tested with virtual fast nicotinic excitatory postsynaptic potentials (EPSPs) created with dynamic clamp. The blocking of Ih with 15 μM ZD7288 hyperpolarized cells by 4.7 mV and increased the virtual synaptic conductance required to stimulate an action potential from 7.0 ± 0.9 nS to 12.1 ± 0.9 nS. In response to stimulation with 40 s long trains of virtual EPSPs, ZD7288 reduced postsynaptic firing from 2.2 to 1.7 Hz and the associated synaptic amplification from 2.2 ± 0.1 to 1.7 ± 0.2. Cyclic nucleotide binding to HCN channels was simulated by blocking native Ih with ZD7288, followed by reconstitution with virtual Ih using a dynamic clamp model of the voltage clamp data. Over a 30-mV range, shifting the half-activation voltage for Ih in 10 mV depolarizing increments always increased synaptic gain. These results indicate that Ih, in sympathetic neurons, can strengthen nicotinic EPSPs and increase synaptic amplification, while also working as a substrate for cyclic nucleotide-dependent modulation.

Unusual Intranuclear Structures in Chick Sympathetic Neurons

1967 ◽  
Vol 25 ◽  
pp. 188-189
Author(s):  
E. B. Masurovsky ◽  
H. H. Benitez ◽  
M. R. Murray
Keyword(s):  
Electron Microscope ◽  
Sympathetic Neurons ◽  
Uranyl Acetate ◽  
Sympathetic Ganglia ◽  
Lead Citrate ◽  
Thin Sections ◽  
Cns Neurons ◽  
Mammalian Cns

Recent light- and electron microscope studies concerned with the effects of D2O on the development of chick sympathetic ganglia in long-term, organized culture revealed the presence of rod-like fibrillar formations, and associated granulofibrillar bodies, in the nuclei of control and deuterated neurons. Similar fibrillar formations have been reported in the nuclei of certain mammalian CNS neurons; however, related granulofibrillar bodies have not been previously described. Both kinds of intranuclear structures are observed in cultures fixed either in veronal acetate-buffered 2%OsO4 (pH 7. 4), or in 3.5% glutaraldehyde followed by post-osmication. Thin sections from such Epon-embedded cultures were stained with ethanolic uranyl acetate and basic lead citrate for viewing in the electron microscope.

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