Serotonin modulates spike probability in the axon initial segment through HCN channels.
The axon initial segment (AIS) serves as the site of action potential initiation in most neurons, but difficulties in isolating the effects of voltage-gated ion channels in the AIS from those of the soma and dendrites have hampered understanding how AIS properties influence neural coding. Here we have combined confocal microscopy, patch-clamp recordings and light-sensitive channel blockers ('photoswitches') in binaural auditory gerbil neurons to show that hyperpolarization and cyclic-nucleotide-gated (HCN) channels are expressed in the AIS and decrease spike probability, in a manner distinct from that of HCN channels in the soma and dendrites. Furthermore, the control of spike threshold by HCN channels in the AIS can be altered through serotonergic modulation of 5-hydroxytryptamine 1A (5-HT1A) receptors, which hyperpolarizes the activation range of HCN channels. As release of serotonin signals changes in motivation and attention states, axonal HCN channels provide a mechanism to translate these signals into changes in the threshold for sensory stimuli.
Department of Neuroscience, University of Texas at Austin, Austin, Texas, USA.|Center for Learning and Memory, University of Texas at Austin, Austin, Texas, USA.
Kwang Woo
KW
Ko
Department of Neuroscience, Baylor College of Medicine, Houston, Texas, USA.
Matthew N
MN
Rasband
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California, USA.
Victor
V
Meseguer
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California, USA.
Richard H
RH
Kramer
Department of Neuroscience, University of Texas at Austin, Austin, Texas, USA.|Center for Learning and Memory, University of Texas at Austin, Austin, Texas, USA.
Nace L
NL
Golding
D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D000071040:Axon Initial Segment / Q000378:metabolism*; D001369:Axons / Q000502:physiology; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000378:metabolism*; D003712:Dendrites / Q000502:physiology; D005849:Gerbillinae; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels / Q000378:metabolism*; D018408:Patch-Clamp Techniques / Q000379:methods; D012701:Serotonin / Q000378:metabolism*
D054815:Cyclic Nucleotide-Gated Cation Channels; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D012701:Serotonin