Selective Modulation of Axonal Sodium Channel Subtypes by 5-HT1A Receptor in Cortical Pyramidal Neuron.
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.
Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China.
Luping
L
Yin
State Key Laboratory of Cognitive Neuroscience and Learning and IDG/McGovern Institute for Brain Research, School of Brain and Cognitive Sciences, the Collaborative Innovation Center for Brain Science.
Malte J
MJ
Rasch
State Key Laboratory of Cognitive Neuroscience and Learning and IDG/McGovern Institute for Brain Research, School of Brain and Cognitive Sciences, the Collaborative Innovation Center for Brain Science.
Quansheng
Q
He
State Key Laboratory of Cognitive Neuroscience and Learning and IDG/McGovern Institute for Brain Research, School of Brain and Cognitive Sciences, the Collaborative Innovation Center for Brain Science.
Si
S
Wu
College of Life Sciences, Beijing Normal University, Beijing 100875, China.
Fei
F
Dou
State Key Laboratory of Cognitive Neuroscience and Learning and IDG/McGovern Institute for Brain Research, School of Brain and Cognitive Sciences, the Collaborative Innovation Center for Brain Science.
Yousheng
Y
Shu
D000818:Animals; D000071040:Axon Initial Segment / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D017397:Prefrontal Cortex / Q000378:metabolism*; D017966:Pyramidal Cells / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D015222:Sodium Channels / Q000378:metabolism*
D015222:Sodium Channels; D044282:Receptor, Serotonin, 5-HT1A
5-HT1A receptor; Nav1.2; Nav1.6; action potential; axon initial segment