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  • Title: Selective Modulation of Axonal Sodium Channel Subtypes by 5-HT1A Receptor in Cortical Pyramidal Neuron.
    Author: Yin L, Rasch MJ, He Q, Wu S, Dou F, Shu Y.
    Journal: Cereb Cortex; 2017 Jan 01; 27(1):509-521. PubMed ID: 26494800.
    Abstract:
    Serotonergic innervation of the prefrontal cortex (PFC) modulates neuronal activity and PFC functions. However, the cellular mechanism for serotonergic modulation of neuronal excitability remains unclear. We performed patch-clamp recording at the axon of layer-5 pyramidal neurons in rodent PFC slices. We found surprisingly that the activation of 5-HT1A receptors selectively inhibits Na+ currents obtained at the axon initial segment (AIS) but not those at the axon trunk. In addition, Na+ channel subtype NaV1.2 but not NaV1.6 at the AIS is selectively modulated by 5-HT1A receptors. Further experiments revealed that the inhibitory effect is attributable to a depolarizing shift of the activation curve and a facilitation of slow inactivation of AIS Na+ currents. Consistently, dual somatic and axonal recording and simulation results demonstrate that the activation of 5-HT1A receptors could decrease the success rate of action potential (AP) backpropagation toward the somatodendritic compartments, enhancing the segregation of axonal and dendritic activities. Together, our results reveal a selective modulation of NaV1.2 distributed at the proximal AIS region and AP backpropagation by 5-HT1A receptors, suggesting a potential mechanism for serotonergic regulation of functional polarization in the dendro-axonal axis, synaptic plasticity and PFC functions.
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