Publications (2)16.17 Total impact
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Article: Dopaminergic Modulation of Axonal Potassium Channel and Action Potential Waveform in Pyramidal Neurons of Prefrontal Cortex.
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ABSTRACT: Voltage-gated K(+) channels (KV) play critical roles in shaping neuronal signals. KV channels distributed at perisomatic regions and thick dendrites of cortical pyramidal neurons have been extensively studied, however the property and regulation of KV channels distributed at the thin axons remained unknown. In this study, by performing somatic and axonal patch-clamp recordings from layer-5 pyramidal neurons of prefrontal cortical slices, we show that the rapidly inactivating A-currents mediated the transient K(+) currents evoked by action potential (AP) waveform command (KAP) at the soma, whereas the rapidly activating but slowly inactivating KV1-mediated D-currents dominated the KAP at the axon. In addition, activation of D1-like receptors of dopamine decreased the axonal K(+) currents, resulting from an increase in the activity of cAMP/PKA pathway. In contrast, activation of D2-like receptors showed an opposite effect on the axonal K(+) currents. Further experiments demonstrated that functional D1-like receptors were expressed at the main axon trunk and their activation could broaden the waveforms of axonal APs. Together, these results show that axonal KV channels were subjected to dopamine modulation, and this modulation could regulate the waveforms of propagating APs at the axon, suggesting an important role of dopaminergic modulation of axonal KV channels in regulating neuronal signaling.The Journal of Physiology 04/2013; · 4.72 Impact Factor -
Article: Enhancement of asynchronous release from fast-spiking interneuron in human and rat epileptic neocortex.
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ABSTRACT: Down-regulation of GABAergic inhibition may result in the generation of epileptiform activities. Besides spike-triggered synchronous GABA release, changes in asynchronous release (AR) following high-frequency discharges may further regulate epileptiform activities. In brain slices obtained from surgically removed human neocortical tissues of patients with intractable epilepsy and brain tumor, we found that AR occurred at GABAergic output synapses of fast-spiking (FS) neurons and its strength depended on the type of connections, with FS autapses showing the strongest AR. In addition, we found that AR depended on residual Ca²⁺ at presynaptic terminals but was independent of postsynaptic firing. Furthermore, AR at FS autapses was markedly elevated in human epileptic tissue as compared to non-epileptic tissue. In a rat model of epilepsy, we found similar elevation of AR at both FS autapses and synapses onto excitatory neurons. Further experiments and analysis showed that AR elevation in epileptic tissue may result from an increase in action potential amplitude in the FS neurons and elevation of residual Ca²⁺ concentration. Together, these results revealed that GABAergic AR occurred at both human and rat neocortex, and its elevation in epileptic tissue may contribute to the regulation of epileptiform activities.PLoS Biology 05/2012; 10(5):e1001324. · 11.45 Impact Factor
