PubMed Health⌕ Search

Biomedical subjects

B X Gao

Publications and source records attributed to B X Gao.

8 recordsLinked to original sources

Development of spontaneous synaptic transmission in the rat spinal cord.

Dorsal root afferents form synaptic connections on motoneurons a few days after motoneuron clustering in the rat lumbar spinal cord, but frequent spontaneous synaptic potentials are detected only after birth. To increase our understanding of the mechanisms underlying the differentiation of synaptic transmission, we examined the developmental changes in properties of spontaneous synaptic transmission at early stages of synapse formation. Spontaneous postsynaptic currents (PSCs) and tetrodotoxin (TTX)-resistant miniature PSCs (mPSCs) were measured in spinal motoneurons of embryonic and postnatal rats using whole cell patch-clamp recordings. Spontaneous PSC frequencies were higher than mPSC frequencies in both embryonic and postnatal motoneurons, suggesting that even at embryonic stages, when action-potential firing rate was low, presynaptic action potentials played an important role in triggering spontaneous PSCs. After birth, the twofold increase in spontaneous PSC frequency was attributed to an increase in action-potential-independent quantal release rather than to a higher rate of action-potential firing. In embryonic motoneurons, the fluctuations in peak amplitude of spontaneous PSCs were normally distributed around single peaks with modal values similar to those of mPSCs. These data indicated that early in synapse differentiation spontaneous PSCs were primarily composed of currents generated by quantal release. After birth, mean mPSC amplitude increased by 50% but mean quantal current amplitude did not change. Synchronous, multiquantal release was apparent in postnatal motoneurons only in high-K+ extracellular solution. Comparison of the properties of miniature excitatory and inhibitory postsynaptic currents (mEPSCs and mIPSCs) demonstrated that mean mEPSC frequency was higher than mIPSC frequency, suggesting that either excitatory synapses outnumbered inhibitory synapses or that the probability of excitatory transmitter release was higher than the release of inhibitory neurotransmitters. The finding that mIPSC duration was several-fold longer than mEPSC duration implied that despite their lower frequency, inhibitory currents could modulate motoneuron synaptic integration by shunting incoming excitatory inputs for prolonged time intervals.

2-Amino-5-phosphonovalerate↗

Development of ionic currents underlying changes in action potential waveforms in rat spinal motoneurons.

Development of ionic currents underlying changes in action potential waveforms in rat spinal motoneurons. J. Neurophysiol. 80: 3047-3061, 1998. Differentiation of the ionic mechanism underlying changes in action potential properties was investigated in spinal motoneurons of embryonic and postnatal rats using whole cell voltage- and current-clamp recordings. Relatively slow-rising, prolonged, largely Na+-dependent action potentials were recorded in embryonic motoneurons, and afterdepolarizing potentials were elicited in response to prolonged intracellular injections of depolarizing currents. Action potential amplitude, as well as its rates of rise and repolarization significantly increased, and an afterhyperpolarizing potential (AHP) became apparent immediately after birth. Concurrently, repetitive action potential firing was elicited in response to a prolonged current injection. To determine the ionic mechanism underlying these changes, the properties of voltage-gated macroscopic Na+, Ca2+, and K+ currents were examined. Fast-rising Na+ currents (INa) and slow-rising Ca2+ currents (ICa) were expressed early in embryonic development, but only INa was necessary and sufficient to trigger an action potential. INa and ICa densities significantly increased while the time to peak INa and ICa decreased after birth. The postnatal increase in INa resulted in overshooting action potential with significantly faster rate of rise than that recorded before birth. Properties of three types of outward K+ currents were examined: transient type-A current (IA), noninactivating delayed rectifier-type current (IK), and Ca2+-dependent K+ current (IK(Ca)). The twofold postnatal increase in IK and IK(Ca) densities resulted in shorter duration action potential and the generation of AHP. Relatively large IA was expressed early in neuronal development, but unlike IK and IK(Ca) its density did not increase after birth. The three types of K+ channels had opposite modulatory actions on action potential firing behavior: IK and IA increased the firing rate, whereas IK(Ca) decreased it. Our findings demonstrated that the developmental changes in action potential waveforms and the onset of repetitive firing were correlated with large increases in the densities of existing voltage-gated ion channels rather than the expression of new channel types.

Action Potentials↗

Development of glycine- and GABA-gated currents in rat spinal motoneurons.

1. Developmental changes in glycine- and gamma-aminobutyric acid (GABA)-activated currents were studied in spinal motoneurons of embryonic and neonatal rats with the use of whole cell recording techniques. 2. Pressure ejection of glycine or GABA onto motoneuron somata produced Cl(-)-mediated inward currents and membrane depolarizations. During embryonic development, the average amplitude of GABA-gated currents was threefold larger than that of glycine-gated currents, but as a result of a large eightfold postnatal increase in glycine-activated currents, similar currents were produced by both amino acids after birth. 3. At all ages the decay of glycine- and GABA-gated currents best fit one-exponential curve, and their time constants were similar. The average decay time constant decreased by twofold after birth. 4. The ionic specificity of glycine- and GABA-gated channels was studied to determine whether the large amplitude of GABA-activated currents in embryonic motoneurons resulted from the contribution of an outward HCO-3 movement. Manipulations of Cl- and HCO-3 concentrations produced changes in the reversal potentials of glycine and GABA that were similar to the calculated changes in the equilibrium potentials of Cl-. This suggested that glycine- and GABA-gated currents were Cl- specific, and HCO-3 movement did not contribute more to the current generated by GABA than that produced by glycine. 5. Glycine- and GABA-gated currents were associated with severalfold increases in membrane conductance. The conductance increase generated by GABA in embryonic motoneurons was sevenfold larger than that generated by glycine, but similar conductance changes were produced by both amino acids after birth.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Development of chemosensitivity in serotonin-deficient spinal cords of rat embryos.

The characteristics of serotonin-induced potentials change during normal development of spinal cords of rat embryos. These changes are temporally correlated with the growth of serotonin projections into the spinal cord. To determine whether serotonin (5-hydroxytryptamine, 5-HT) in the growing projections is responsible for modulating the changes in neuronal responses to 5-HT, 5-HT synthesis was blocked, and motoneuron responses to exogenous 5-HT were studied 1-2 weeks later. Starting at Day 9 of gestation, prior to the generation of 5-HT neurons in the medulla, pregnant rats were injected daily with p-chlorophenylalanine (p-CPA) which suppressed 5-HT synthesis. p-CPA was effective in reducing 5-HT concentrations because immunoreactive 5-HT projections were absent in embryonic spinal cords of p-CPA-treated rats. However, suppression of 5-HT synthesis did not affect the onset and time course of development of 5-HT-induced potentials. Furthermore, in the absence of 5-HT, the potentials generated by 5-HT were significantly larger than those produced in motoneurons of control rats. These findings indicated that the number of receptors or their binding affinity increased in the absence of 5-HT. The increased responses in p-CPA-treated rats were mediated via 5-HT2/5-HT1C receptors, while activation of other 5-HT1 receptor subtypes and 5-HT3 receptors induced similar depolarizations in p-CPA-treated and untreated rats. Our study suggested that 5-HT was not required for the onset of receptor expression in developing spinal neurons, but it may be responsible for receptor down-regulation.

Animals↗

Changes in serotonin-induced potentials during spinal cord development.

1. Motoneuron responses to serotonin (5-hydroxytryptamine, 5-HT), and the growth pattern of 5-HT projections into the ventral horn were studied in the isolated spinal cord of embryonic and neonatal rats. 2. 5-HT projections first appeared in lumbar spinal cord at days 16-17 of gestation (E16-E17) and were localized in the lateral and ventral funiculi. By E18, the projections had grown into the ventral horn, and at 1-2 days after birth they were in close apposition to motoneuron somata. 3. At E16-E17, slow-rising depolarizing potentials of 1-4 mV were recorded intracellularly in lumbar motoneurons in response to bath application of 5-HT. These potentials were not apparent after E18; at that time 5-HT generated long-lasting depolarizations with an average amplitude of 6 mV, and an increase of 11% in membrane resistance. Starting at E18, 5-HT also induced high-frequency fast-rising potentials that were blocked by antagonists of glutamate, gamma-aminobutyric acid, and glycine. 4. Motoneuron responses to 5-HT increased significantly after birth, when 5-HT produced an average depolarization of 19 mV and repetitive firing of action potentials. 5. Tetrodotoxin and high Mg2+ did not reduce the amplitude of the long-lasting depolarizations, which suggested that they were produced by direct action of 5-HT on motoneuron membrane. 6. At all developmental ages, 5-HT reduced the amplitude of dorsal root-evoked potentials. The suppressed responses were neither due to 5-HT-induced depolarization nor the result of a decrease in motoneuron excitability. 7. The pharmacological profile of 5-HT-induced potentials was studied with the use of various agonists and antagonists of 5-HT. The findings indicated that the actions of 5-HT on spinal neurons were mediated via multiple 5-HT receptor subtypes. 8. Our results suggested that 5-HT excited spinal neurons before 5-HT projections grew into the ventral horn. The characteristics of 5-HT-induced potentials changed, however, at the time when the density of 5-HT projections increased in the motor nuclei.

Action Potentials↗