title: Serotonin modulates response properties of neurons in the dorsal cochlear nucleus of the mouse.
abstract: The neurochemical serotonin (5-hydroxytryptamine, 5-HT) is involved in a variety of behavioral functions including arousal, reward, and attention, and has a role in several complex disorders of the brain. In the auditory system, 5-HT fibers innervate a number of subcortical nuclei, yet the modulatory role of 5-HT in nearly all of these areas remains poorly understood. In this study, we examined spiking activity of neurons in the dorsal cochlear nucleus (DCN) following iontophoretic application of 5-HT. The DCN is an early site in the auditory pathway that receives dense 5-HT fiber input from the raphe nuclei and has been implicated in the generation of auditory disorders marked by neuronal hyperexcitability. Recordings from the DCN in awake mice demonstrated that iontophoretic application of 5-HT had heterogeneous effects on spiking rate, spike timing, and evoked spiking threshold. We found that 56% of neurons exhibited increases in spiking rate during 5-HT delivery, while 22% had decreases in rate and the remaining neurons had no change. These changes were similar for spontaneous and evoked spiking and were typically accompanied by changes in spike timing. Spiking increases were associated with lower first spike latencies and jitter, while decreases in spiking generally had opposing effects on spike timing. Cases in which 5-HT application resulted in increased spiking also exhibited lower thresholds compared to the control condition, while cases of decreased spiking had no threshold change. We also found that the 5-HT2receptor subtype likely has a role in mediating increased excitability. Our results demonstrate that 5-HT can modulate activity in the DCN of awake animals and that it primarily acts to increase neuronal excitability, in contrast to other auditory regions where it largely has a suppressive role. Modulation of DCN function by 5-HT has implications for auditory processing in both normal hearing and disordered states.
authors.affiliation: School of Biological Sciences and Integrative Physiology and Neuroscience, Washington State University, Vancouver, WA, USA. Electronic address: rfelix@wsu.edu.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Felix
authors.affiliation: School of Biological Sciences and Integrative Physiology and Neuroscience, Washington State University, Vancouver, WA, USA.
authors.forename: Cameron J
authors.initials: CJ
authors.lastname: Elde
authors.affiliation: School of Biological Sciences and Integrative Physiology and Neuroscience, Washington State University, Vancouver, WA, USA.
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Nevue
authors.affiliation: School of Biological Sciences and Integrative Physiology and Neuroscience, Washington State University, Vancouver, WA, USA.
authors.forename: Christine V
authors.initials: CV
authors.lastname: Portfors
mesh_terms: D000161:Acoustic Stimulation; D000818:Animals; D001307:Auditory Perception / Q000187:drug effects*; D001522:Behavior, Animal / Q000187:drug effects*; D017626:Cochlear Nucleus / Q000187:drug effects* / Q000378:metabolism; D004569:Electroencephalography; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects; D005260:Female; D007478:Iontophoresis; D008297:Male; D008808:Mice, Inbred CBA; D011930:Reaction Time / Q000187:drug effects; D044348:Receptors, Serotonin, 5-HT2 / Q000187:drug effects* / Q000378:metabolism; D059326:Serotonergic Neurons / Q000187:drug effects* / Q000378:metabolism; D012701:Serotonin / Q000008:administration & dosage* / Q000378:metabolism; D058826:Serotonin 5-HT2 Receptor Agonists / Q000008:administration & dosage*; D013997:Time Factors
chemical_list: D044348:Receptors, Serotonin, 5-HT2; D058826:Serotonin 5-HT2 Receptor Agonists; D012701:Serotonin
keywords: 5-HT; Auditory brainstem; DCN; Fusiform cell; Neuromodulation