scholarly journals Heterogeneity of Membrane Properties in Sympathetic Preganglionic Neurons of Neonatal Mice: Evidence of Four Subpopulations in the Intermediolateral Nucleus

2010 ◽  
Vol 103 (1) ◽  
pp. 490-498 ◽  
Author(s):  
Amanda Zimmerman ◽  
Shawn Hochman

Spinal cord sympathetic preganglionic neurons (SPNs) integrate activity from descending and sensory systems to determine the final central output of the sympathetic nervous system. The intermediolateral column (IML) has the highest number and density of SPNs and, within this region, SPN somas are found in distinct clusters within thoracic and upper lumbar spinal segments. Whereas SPNs exhibit a rostrocaudal gradient of end-target projections, individual clusters contain SPNs with diverse functional roles. Here we explored diversity in the electrophysiological properties observed in Hb9-eGFP–identified SPNs in the IML of neonatal mice. Overall, mouse SPN intrinsic membrane properties were comparable with those seen in other species. A wide range of values was obtained for all measured properties (up to a 10-fold difference), suggesting that IML neurons are highly differentiated. Using linear regression we found strong correlations between many cellular properties, including input resistance, rheobase, time constant, action potential shape, and degree of spike accommodation. The best predictor of cell function was rheobase, which correlated well with firing frequency–injected current ( f– I) slopes as well as other passive and active membrane properties. The range in rheobase suggests that IML neurons have a recruitment order with stronger synaptic drives required for maximal recruitment. Using cluster analysis, we identified at least four subpopulations of SPNs, including one with a long time constant, low rheobase, and high f– I gain. We thus propose that the IML contains populations of neurons that are differentiable by their membrane properties and hypothesize they represent diverse functional classes.

1990 ◽  
Vol 63 (2) ◽  
pp. 333-346 ◽  
Author(s):  
R. Nitzan ◽  
I. Segev ◽  
Y. Yarom

1. Intracellular recordings from neurons in the dorsal motor nucleus of the vagus (vagal motoneurons, VMs) obtained in the guinea pig brain stem slice preparation were used for both horseradish peroxidase (HRP) labeling of the neurons and for measurements of their input resistance (RN) and time constant (tau 0). Based on the physiological data and on the morphological reconstruction of the labeled cells, detailed steady-state and compartmental models of VM were built and utilized to estimate the range of membrane resistivity, membrane capacitance, and cytoplasm resistivity values (Rm, Cm, and Ri, respectively) and to explore the integrative properties of these cells. 2. VMs are relatively small cells with a simple dendritic structure. Each cell has an average of 5.3 smooth (nonspiny), short (251 microns) dendrites with a low order (2) of branching. The average soma-dendritic surface area of VMs is 9,876 microns 2. 3. Electrically, VMs show remarkably linear membrane properties in the hyperpolarizing direction; they have an average RN of 67 +/- 23 (SD) M omega and a tau 0 of 9.4 +/- 4.1 ms. Several unfavorable experimental conditions precluded the possibility of faithfully recovering ("peeling") the first equalizing time constant (tau 1) and, thereby, of estimating the electrotonic length (Lpeel) of VMs. 4. Reconciling VM morphology with the measured RN and tau 0 through the models, assuming an Ri of 70 omega.cm and a spatially uniform Rm, yielded an Rm estimate of 5,250 omega.cm2 and a Cm of 1.8 microF/cm2. Peeling theoretical transients produced by these models result in an Lpeel of 1.35. Because of marked differences in the length of dendrites within a single cell, this value is larger than the maximal cable length of the dendrites and is twice as long as their average cable length. 5. The morphological and physiological data could be matched indistinguishably well if a possible soma shunt (i.e., Rm, soma less than Rm, dend) was included in the model. Although there is no unique solution for the exact model Rm, a general conclusion regarding the integrative capabilities of VM could be drawn. As long as the model is consistent with the experimental data, the average input resistance at the dendritic terminals (RT) and the steady-state central (AFT----S) and peripheral (AFS----T) attenuation factors are essentially the same in the different models. With Ri = 70 omega.cm, we calculated RT, AFS----T, and AFT----S to be, on the average, 580 M omega, 1.1, and 13, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)


2004 ◽  
Vol 91 (1) ◽  
pp. 571-575 ◽  
Author(s):  
Jason J. Kuo ◽  
Martijn Schonewille ◽  
Teepu Siddique ◽  
Annet N. A. Schults ◽  
Ronggen Fu ◽  
...  

ALS (amyotrophic lateral sclerosis) is an adult-onset and deadly neurodegenerative disease characterized by a progressive and selective loss of motoneurons. Transgenic mice overexpressing a mutated human gene (G93A) coding for the enzyme SOD1 (Cu/Zn superoxide dismutase) develop a motoneuron disease resembling ALS in humans. In this generally accepted ALS model, we tested the electrophysiological properties of individual embryonic and neonatal spinal motoneurons in culture by measuring a wide range of electrical properties influencing motoneuron excitability during current clamp. There were no differences in the motoneuron resting potential, input conductance, action potential shape, or afterhyperpolarization between G93A and control motoneurons. The relationship between the motoneuron's firing frequency and injected current (f-I relation) was altered. The slope of the f-I relation and the maximal firing rate of the G93A motoneurons were much greater than in the control motoneurons. Differences in spontaneous synaptic input were excluded as a cause of increased excitability. This finding identifies a markedly elevated intrinsic electrical excitability in cultured embryonic and neonatal mutant G93A spinal motoneurons. We conclude that the observed intrinsic motoneuron hyperexcitability is induced by the SOD1 toxic gain-of-function through an aberration in the process of action potential generation. This hyperexcitability may play a crucial role in the pathogenesis of ALS as the motoneurons were cultured from presymptomatic mice.


2019 ◽  
Vol 20 (6) ◽  
pp. 1416 ◽  
Author(s):  
Aniello Lombardi ◽  
Peter Jedlicka ◽  
Heiko Luhmann ◽  
Werner Kilb

The effects of ionotropic γ-aminobutyric acid receptor (GABA-A, GABAA) activation depends critically on the Cl−-gradient across neuronal membranes. Previous studies demonstrated that the intracellular Cl−-concentration ([Cl−]i) is not stable but shows a considerable amount of activity-dependent plasticity. To characterize how membrane properties and different molecules that are directly or indirectly involved in GABAergic synaptic transmission affect GABA-induced [Cl−]i changes, we performed compartmental modeling in the NEURON environment. These simulations demonstrate that GABA-induced [Cl−]i changes decrease at higher membrane resistance, revealing a sigmoidal dependency between both parameters. Increase in GABAergic conductivity enhances [Cl−]i with a logarithmic dependency, while increasing the decay time of GABAA receptors leads to a nearly linear enhancement of the [Cl−]i changes. Implementing physiological levels of HCO3−-conductivity to GABAA receptors enhances the [Cl−]i changes over a wide range of [Cl−]i, but this effect depends on the stability of the HCO3− gradient and the intracellular pH. Finally, these simulations show that pure diffusional Cl−-elimination from dendrites is slow and that a high activity of Cl−-transport is required to improve the spatiotemporal restriction of GABA-induced [Cl−]i changes. In summary, these simulations revealed a complex interplay between several key factors that influence GABA-induced [Cl]i changes. The results suggest that some of these factors, including high resting [Cl−]i, high input resistance, slow decay time of GABAA receptors and dynamic HCO3− gradient, are specifically adapted in early postnatal neurons to facilitate limited activity-dependent [Cl−]i decreases.


1992 ◽  
Vol 70 (S1) ◽  
pp. S92-S97 ◽  
Author(s):  
Hiroe Inokuchi ◽  
Megumu Yoshimura ◽  
Canio Polosa ◽  
Syogoro Nishi

Intracellular recordings were made from 168 sympathetic preganglionic neurons in the slice of the second or third thoracic spinal-cord segment of the adult cat to study the actions of noradrenaline on these neurons. Noradrenaline, applied by superfusion (0.5–50 μM), produced membrane depolarization in 73 neurons and membrane hyperpolarization in 39 neurons. In 26 neurons noradrenaline produced a biphasic response (depolarization–hyperpolarization or vice versa). The depolarization was blocked by prazosin, while the hyperpolarization was blocked by yohimbine. The noradrenaline-induced depolarization was associated with an increase in neuron input resistance, while the noradrenaline-induced hyperpolarization was associated with a decrease in neuron input resistance. Both responses decreased in amplitude with membrane hyperpolarization and were nullified at around the potassium equilibrium potential EK. The null potential of both responses became more and less negative with a decrease and an increase, respectively, in the extracellular potassium concentration. When the membrane potential was made more negative than EK, the noradrenaline-induced hyperpolarization reversed to depolarization in all cases, whereas in only 4 of 12 cases did the noradrenaline-induced depolarization reverse to hyperpolarization. These data suggest that the noradrenaline-induced depolarization is a result of a decrease, while the noradrenaline-induced hyperpolarization is a result of an increase in K+ conductance. Cobalt (2 mM), low calcium – high magnesium, and intracellular EGTA markedly reduced or abolished the noradrenaline-induced depolarization but had no significant effect on the noradrenaline-induced hyperpolarization. Barium (2 mM) depressed both responses. Tetraethylammonium (10–30 mM), 4-aminopyridine (3 mM), and cesium (2 mM) had no effect on either response. These data suggest that the noradrenaline-induced depolarization is a result of an inactivation of a background calcium-sensitive K+ conductance, while the noradrenaline-induced hyperpolarization is due to activation of a calcium-insensitive potassium conductance.Key words: K+ conductances, catecholamines, Ca2+ dependent, K+ current, spinal cord.


1973 ◽  
Vol 51 (1) ◽  
pp. 29-38 ◽  
Author(s):  
Issie Wyszogrodski ◽  
Canio Polosa

The inhibitory effect of sciatic and ulnar nerve afferent stimulation on the firing frequency of sympathetic preganglionic neurons was studied in anesthetized or unanesthetized decerebrate cats, with intact spinal cords or with spinal cords sectioned at C2. The spontaneous firing and the firing evoked by antidromic stimulation, by iontophoretic glutamate, and by mechanical injury could be depressed, in the preparations both with intact and sectioned spinal cord. The depression was not preceded by excitation. The minimum stimulus strength required for the inhibition was, on average, 15 times the nerve threshold. The inhibition elicited by single shocks lasted several hundred milliseconds and was longer in the intact than in the spinal preparation. The results show that the neural pathway used by high threshold somatic afferents for inhibition of the sympathetic preganglionic neurons is complete within the spinal cord and suggest that the inhibition is probably acting on the preganglionic neuron membrane.


1999 ◽  
Vol 82 (1) ◽  
pp. 209-215 ◽  
Author(s):  
David F. Donnelly

Carotid body chemoreceptors increase their responsiveness to hypoxia in the postnatal period, but the mechanism for this increase is unresolved. The purpose of the present study was to examine developmental changes in cellular characteristics of chemoreceptor afferent neurons in the petrosal ganglia with the underlying hypothesis that developmental changes occur and may account for the developmental increase in chemoreceptor responsiveness. Chemoreceptor complexes (carotid body, sinus nerve, glossopharyngeal nerve, and petrosal ganglia) were harvested from rats, aged 3–40 days, and intracellular recordings were obtained from petrosal ganglion neurons using sharp electrode impalement. All chemoreceptor neurons across ages were C fibers with conduction velocities <1 m/s and generated repetitive action potentials with depolarization. Resting membrane potential was −61.3 ± 0.9 (SE) mV ( n = 78) and input resistance was 108 ± 6 MΩ and did not significantly change with age. Cell capacitance was 32.4 ± 1.7 pF and did not change with age. Rheobase averaged 0.21 ± 0.02 nA and slightly increased with age. Action potentials were followed by an afterhyperpolarization of 12.4 ± 0.6 mV and time constant 6.9 ± 0.5 ms; only the time constant decreased with age. These results, obtained in rat, demonstrate electrophysiologic characteristics which differ substantially from that previously described in cat chemoreceptor neurons. In general developmental changes in cell characteristics are small and are unlikely to account for the developmental increase in chemoreceptor responsiveness with age.


2006 ◽  
Vol 95 (4) ◽  
pp. 2492-2500 ◽  
Author(s):  
Andrew D. Whyment ◽  
Andrew M. Blanks ◽  
Kevin Lee ◽  
Leo P. Renaud ◽  
David Spanswick

The role of histamine in regulating excitability of sympathetic preganglionic neurons (SPNs) and the expression of histamine receptor mRNA in SPNs was investigated using whole-cell patch-clamp electrophysiological recording techniques combined with single-cell reverse transcriptase polymerase chain reaction (RT-PCR) in transverse neonatal rat spinal cord slices. Bath application of histamine (100 μM) or the H1 receptor agonist histamine trifluoromethyl toluidide dimaleate (HTMT; 10 μM) induced membrane depolarization associated with a decrease in membrane conductance in the majority (70%) of SPNs tested, via activation of postsynaptic H1 receptors negatively coupled to one or more unidentified K+ conductances. Histamine and HTMT application also induced or increased the amplitude and/or frequency of membrane potential oscillations in electrotonically coupled SPNs. The H2 receptor agonist dimaprit (10 μM) or the H3 receptor agonist imetit (100 nM) were without significant effect on the membrane properties of SPNs. Histamine responses were sensitive to the H1 receptor antagonist triprolidine (10 μM) and the nonselective potassium channel blocker barium (1 mM) but were unaffected by the H2 receptor antagonist tiotidine (10 μM) and the H3 receptor antagonist, clobenpropit (5 μM). Single cell RT-PCR revealed mRNA expression for H1 receptors in 75% of SPNs tested, with no expression of mRNA for H2, H3, or H4 receptors. These data represent the first demonstration of H1 receptor expression in SPNs and suggest that histamine acts to regulate excitability of these neurons via a direct postsynaptic effect on H1 receptors.


2009 ◽  
Vol 102 (2) ◽  
pp. 774-785 ◽  
Author(s):  
Meijun Ye ◽  
Abdallah Hayar ◽  
Edgar Garcia-Rill

Parafascicular (Pf) neurons receive cholinergic input from the pedunculopontine nucleus (PPN), which is active during waking and REM sleep. There is a developmental decrease in REM sleep in humans between birth and puberty and 10–30 days in rat. Previous studies have established an increase in muscarinic and 5-HT1 serotonergic receptor–mediated inhibition and a transition from excitatory to inhibitory GABAA responses in the PPN during the developmental decrease in REM sleep. However, no studies have been conducted on the responses of Pf cells to the cholinergic input from the PPN during development, which is a major target of ascending cholinergic projections and may be an important mechanism for the generation of rhythmic oscillations in the cortex. Whole cell patch-clamp recordings were performed in 9- to 20-day-old rat Pf neurons in parasagittal slices, and responses to the cholinergic agonist carbachol (CAR) were determined. Three types of responses were identified: inhibitory (55.3%), excitatory (31.1%), and biphasic (fast inhibitory followed by slow excitatory, 6.8%), whereas 6.8% of cells showed no response. The proportion of CAR-inhibited Pf neurons increased with development. Experiments using cholinergic antagonists showed that M2 receptors mediated the inhibitory response, whereas excitatory modulation involved M1, nicotinic, and probably M3 or M5 receptors, and the biphasic response was caused by the activation of multiple types of muscarinic receptors. Compared with CAR-inhibited cells, CAR-excited Pf cells showed 1) a decreased membrane time constant, 2) higher density of hyperpolarization-activated channels ( Ih), 3) lower input resistance ( Rin), 4) lower action potential threshold, and 5) shorter half-width duration of action potentials. Some Pf cells exhibited spikelets, and all were excited by CAR. During development, we observed decreases in Ih density, Rin, time constant, and action potential half-width. These results suggest that cholinergic modulation of Pf differentially affects separate populations, perhaps including electrically coupled cells. Pf cells tend to show decreased excitability and cholinergic activation during the developmental decrease in REM sleep.


1987 ◽  
Vol 57 (3) ◽  
pp. 633-644 ◽  
Author(s):  
S. J. Redman ◽  
E. M. McLachlan ◽  
G. D. Hirst

We have studied the passive membrane properties of sympathetic neurons in isolated lumbar paravertebral ganglia of young rats by recording the voltage response to small steps of current passed through an intracellular microelectrode. Substitution of Ba2+ (2.5 mM) for Ca2+ (2.5 mM) in the bathing solution increased the input resistance and the time constant of the voltage response, but the increase in time constant was disproportionately large relative to the increase in input resistance. After consideration of the passive electrical properties and the geometry of the soma and dendrites, it was concluded that the disproportionate change in input resistance and time constant could be explained if barium inactivated a resting potassium conductance that was concentrated in the distal dendrites. In the APPENDIX, the effect of nonuniform membrane conductance on the relationship between input resistance and time constant in models of these neurons is analyzed.


Sign in / Sign up

Export Citation Format

Share Document