scholarly journals Developmental regulation of membrane excitability in rat spinal lamina I projection neurons

2012 ◽  
Vol 107 (10) ◽  
pp. 2604-2614 ◽  
Author(s):  
Jie Li ◽  
Mark L. Baccei

It is now universally recognized that neonates can experience considerable pain. While spinal lamina I neurons projecting to the brain contribute to the generation of hyperalgesia, nothing is known about their electrophysiological properties during early life. Here we have used in vitro whole cell patch-clamp recordings in rat spinal cord slices to determine whether the intrinsic membrane properties of lamina I projection neurons, as well as their synaptic inputs, are developmentally regulated during the early postnatal period. Projection neurons were identified via retrograde transport of DiI injected into the parabrachial nucleus (PB) or periaqueductal gray (PAG) and characterized at postnatal days (P)2–5, P10–12, P19–23, and P30–32. Both spino-PB and spino-PAG neurons demonstrated an age-dependent reduction in spike threshold and duration at room temperature, which was accompanied by a developmental increase in the frequency of miniature excitatory and inhibitory postsynaptic currents. Notably, in both groups, age-dependent changes in the passive membrane properties or rheobase only occurred after the third postnatal week. However, spontaneous activity was significantly more prevalent within the developing spino-PB population and was dominated by an irregular pattern of discharge. In addition, while the instantaneous firing frequency remained unaltered in spino-PB neurons during the first weeks of life, spino-PAG cells fired at a higher rate at P19–23 compared with younger groups, suggesting that the gain of parallel ascending nociceptive pathways may be independently regulated during development. Overall, these results demonstrate that intrinsic membrane excitability is modulated in a cell type-specific manner within developing spinal nociceptive circuits.

1990 ◽  
Vol 63 (4) ◽  
pp. 663-675 ◽  
Author(s):  
P. Calabresi ◽  
N. B. Mercuri ◽  
G. Bernardi

1. The effects of intrinsic membrane properties on the spontaneous and synaptically evoked activity of neostriatal neurons were studied in an in vitro slice preparation with the use of intracellular recordings. The recorded neurons did not show spontaneous action potentials at rest; depolarizing current pulses triggered a tonic firing pattern. 2. Subthreshold spontaneous depolarizing potentials (SDPs) were observed in 52% of the recorded neurons. The amplitude of these potentials at rest ranged between 2 and 15 mV, and their duration between 4 and 100 ms. The frequency and the amplitude of the SDPs were functions of the membrane potential: membrane depolarization by constant positive current increased the frequency of the SDPs and reduced their amplitude; hyperpolarization of the membrane decreased their frequency and increased their amplitude. Often, at membrane potentials more negative than -90 mV, SDPs were completely suppressed. 3. SDPs were blocked by low calcium-cobalt containing solutions. In the presence of tetrodotoxin (TTX, 1-3 microM), SDPs were completely abolished in 50% of the tested neurons; in the remaining neurons, small (1-4 mV) TTX-resistant SDPs were observed. In most of the neurons, bicuculline (BIC, 10-100 microM) and low concentrations of tetanus toxin (5-10 micrograms/ml) did not clearly affect the SDPs. Higher concentrations of tetanus toxin (100 micrograms/ml) blocked the SDPs as well as the synaptic potentials evoked by intrastriatal stimulation. 4. At resting membrane potential, intrastriatal stimulation produced a fast depolarizing postsynaptic potential (EPSP) that was reduced by BIC (10-100 microM). The relationship between EPSP amplitude and membrane potential was studied either by utilizing K(+)-chloride electrodes or by the use of cesium-chloride electrodes. In both these cases, the reversal potential for the EPSPs was between 0 and -14 mV. In cesium-loaded neurons, the decrease of the EPSP, usually observed at negative membrane potentials (below -85 mV), was clearly reduced. Internal cesium prolonged the duration of the SDPs and the EPSPs evoked by intrastriatal stimulation. 5. The relationship between spontaneous and evoked synaptic activity and membrane potential was studied in the presence of different external potassium blockers. 4-Aminopyridine (4AP, 0.1-1 mM) increased the EPSP amplitude and the frequency of the SDPs, but did not decrease membrane rectification and the shunt of the EPSPs present at negative membrane potentials. On the contrary, rectification of the membrane and the shunt of the EPSPs below -85 mV were clearly reduced by tetraethylammonium (TEA, 10-20 mM).(ABSTRACT TRUNCATED AT 400 WORDS)


Neuroscience ◽  
2006 ◽  
Vol 141 (2) ◽  
pp. 977-988 ◽  
Author(s):  
R. Ruscheweyh ◽  
A. Goralczyk ◽  
G. Wunderbaldinger ◽  
A. Schober ◽  
J. Sandkühler

1982 ◽  
Vol 243 (6) ◽  
pp. E512-E521 ◽  
Author(s):  
R. L. Ruff ◽  
D. Martyn ◽  
A. M. Gordon

We explored the possibility that glucocorticoid-induced muscle weakness and atrophy resulted from impaired muscle membrane excitability. Male Sprague-Dawley rats received intramuscular injections of dexamethasone, cortisone acetate (equivalent anti-inflammatory doses), or saline for up to 28 days. Temporal patterns of change in muscle mass, twitch and tetanic tension, and membrane potential, cable parameters, and excitability were studied in vitro in the extensor digitorum longus (EDL), soleus (SOL), omohyoid (OMO), caudofemoralis (CF), and the sternomastoid muscles (membrane potential only). the membrane properties of EDL fibers were also studied in vivo (pentobarbital anesthesia). The relative severity of atrophy was OMO greater than CF greater than EDL greater than SOL. Reduction in twitch or tetanic tension never preceded atrophy. The twitch and tetanic tension (per g muscle) increased with glucocorticoid treatment. There were no significant changes in the time course of the twitch or tetanus. Dexamethasone produced more severe atrophy and force reduction than did cortisone acetate. Glucocorticoid treatment produced a depolarization of EDL muscle fibers measured in vitro at 23 degrees C, but this did not appear to be physiologically significant because EDL fibers studied in vivo were not depolarized and had normal action potential amplitudes and thresholds. Glucocorticoid treatment did not change the membrane resistance or capacitance. We conclude that glucocorticoid treatment did not produce muscle weakness by impairing sarcolemmal excitability or excitation-contraction coupling, but that the weakness resulted from muscle atrophy.


2005 ◽  
Vol 93 (3) ◽  
pp. 1145-1157 ◽  
Author(s):  
Zixiu Xiang ◽  
Lie Wang ◽  
Stephen T. Kitai

The subthalamic nucleus (STN) is considered to be one of the driving forces in the basal ganglia circuit. The STN is innervated by serotonergic afferents from the raphe nucleus and expresses a variety of 5-HT receptor subtypes. We investigated the effects of 5-HT and 5-HT receptor subtype agonists and antagonists on the firing properties of STN neurons in rat brain slices. We used cell-attached, perforated-patch, and whole cell recording techniques to detect changes in firing frequency and pattern and electrical membrane properties. Due to the depolarization of membrane potential caused by reduced potassium conductance, 5-HT (10 μM) increased the firing frequency of STN neurons without changing their firing pattern. Cadmium failed to occlude the effect of 5-HT on firing frequency. 5-HT had no effect on afterhyperpolarization current. These results indicated that the 5-HT action was not mediated by high-voltage–activated calcium channel currents and calcium-dependent potassium currents. 5-HT had no effect on hyperpolarization-activated cation current ( IH) amplitude and voltage-dependence of IH activation, suggesting that IH was not involved in 5-HT–induced excitation. The increased firing by 5-HT was mimicked by 5-HT2/4 receptor agonist α-methyl-5-HT and was partially mimicked by 5-HT2 receptor agonist DOI or 5-HT4 receptor agonist cisapride. The 5-HT action was partially reversed by 5-HT4 receptor antagonist SB 23597-190, 5-HT2 receptor antagonist ketanserin, and 5-HT2C receptor antagonist RS 102221. Our data indicate that 5-HT has significant ability to modulate membrane excitability in STN neurons; modulation is accomplished by decreasing potassium conductance by activating 5-HT4 and 5-HT2C receptors.


2021 ◽  
Author(s):  
Kumiko Ogata ◽  
Fuko Kadono ◽  
Yasuharu Hirai ◽  
Ken-ichi Inoue ◽  
Masahiko Takada ◽  
...  

The striatum is one of the key nuclei for adequate control of voluntary behaviors and reinforcement learning. Two striatal projection neuron types, expressing either dopamine receptor D1 (D1R) or dopamine receptor D2 (D2R) constitute two independent output routes: the direct or indirect pathways, respectively. These pathways co-work in balance to achieve coordinated behavior. Two projection neuron types are equivalently intermingled in most striatal space. However, recent studies revealed two atypical zones in the caudal striatum: the zone in which D1R-neurons are the minor population (D1R-poor zone) and that in which D2R-neurons are the minority (D2R-poor zone). It remains obscure as to whether these imbalanced zones have similar properties on axonal projections and electrophysiology to other striatal regions. Based on morphological experiments in mice using immunofluorescence, in situ hybridization, and neural tracing, here, we revealed the poor zones densely projected to the globus pallidus and substantia nigra pars lateralis, with a few collaterals in substantia nigra pars reticulata and compacta. As other striatal regions, D1R-neurons were the direct pathway neurons, while projection neurons in the poor zones possessed similar electrophysiological membrane properties to those in the conventional striatum using in vitro electrophysiological recording. In addition, the poor zones existed irrespective of the age of mice. We also identified the poor zones in the common marmoset as well as other rodents. These results suggest that the poor zones in the caudal striatum follow the conventional projection patterns irrespective of imbalanced distribution of projection neurons. The poor zones could be an innate structure and common in mammals and relate to specific functions via highly restricted projections.


1997 ◽  
Vol 77 (6) ◽  
pp. 2910-2924 ◽  
Author(s):  
C. F. Hsiao ◽  
P. R. Trueblood ◽  
M. S. Levine ◽  
S. H. Chandler

Hsiao, C. F., P. R. Trueblood, M. S. Levine, and S. H. Chandler. Multiple effects of serotonin on membrane properties of trigeminal motoneurons in vitro. J. Neurophysiol. 77: 2910–2924, 1997. Intracellular recordings from guinea pig trigeminal motoneurons (TMNs) in brain stem slices were used to determine the underlying ionic mechanisms responsible for our previously demonstrated enhancement of TMN excitability during jaw movements by serotonin (5-HT). 5-HT (0.5–100 μM) depolarized motoneurons and increased input resistance in the majority of neurons tested. Additionally, 5-HT reduced the amplitude of the postspike medium-duration afterhyperpolarization, decreased the current threshold for maintained spike discharge, and increased the maximum slope of the steady-state spike frequency-current relationship. Under voltage clamp, from holding potentials close to resting potential, 5-HT produced an inward current and a decrease in instantaneous slope conductance, suggesting a reduction in a resting K+ leak conductance ( I leak). The instantaneous current-voltage ( I-V) relationship for the inward 5-HT current ( I 5-HT) was linear throughout most of the voltage range tested. However, the steady-state I-V relationship showed some degree of inward rectification at potentials starting around −70 mV. The mean reversal potential for the instantaneous I 5-HT was −86.2 ± 4.5 (SE) mV ( n = 9), a value slightly negative to the predicted potassium equilibrium potential of −82 mV in these neurons. In the presence of 2 mM Ba2+, 5-HT application did not produce a further reduction in input conductance, but did expose a Ba2+-insensitive residual inward current that was resistant to Cs+ application. The instantaneous I-V relationship during 5-HT application in the presence of Ba2+ was shifted downward and parallel to control, suggesting that Ba2+ and 5-HT block the same resting I leak. The residual Ba2+- and Cs+-insensitive component of the total inward I 5-HT was voltage independent and was blocked when the extracellular Na+ was replaced by choline, suggesting that the predominant charge carrier for this residual current is Na+. 5-HT enhanced a hyperpolarization-activated cationic current, I h. In the presence of Ba2+, the time course of I 5-HT resembled that of I h and showed a similar voltage dependence that was blocked by extracellular Cs+ (1–3 mM). The effects of 5-HT on membrane potential, input resistance, and I h were partially mimicked by 5-HT2 agonists and suppressed by 5-HT2 antagonists. It is concluded that 5-HT enhances TMN membrane excitability through modulation of multiple intrinsic membrane conductances. This provides for a mechanism(s) to fine tune the input-output discharge properties of these neurons, thus providing them with greater flexibility in output in response to time-varying synaptic inputs during various movements of the jaw.


1996 ◽  
Vol 76 (4) ◽  
pp. 2794-2798 ◽  
Author(s):  
V. Morisset ◽  
F. Nagy

1. Intracellular recordings were obtained from 111 dorsal horn neurons in lamina V, in an in vitro transverse spinal cord slice preparation of the cervical region from young rats. 2. Of these neurons, 28% showed voltage-dependent plateau potentials, mainly underlain by a tetrodotoxin-resistant dihydropyridine-sensitive Ca2+ current. When depolarized, neurons with plateau properties produced accelerating firing frequency, afterdischarge, and bistability. They also exhibited windup of action potentials when stimulated by repetitive intracellular injections of current. 3. Glutamate being the main excitatory transmitter released by primary afferents, we also considered the effects of specific agonists of metabotropic glutamate receptors and showed that they modulate positively (induce or enhance) plateau properties in the deep dorsal horn neurons.


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