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-HT2 receptor 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.

5-HT1A receptor, 5-HT2A receptor and serotonin transporter binding in the human auditory cortex in depression

“…6,10,11 Furthermore, a similar finding in postmortem tissue of patients with schizophrenia has been reported. 36 While modulation of auditory responses by 5-HT has been observed as early in the auditory processing pathway as the inferior colliculus, [37][38][39][40] our finding also suggests that modulation of auditory cortical responses is not merely carried forward from lower processing regions. To date, the receptors and specific cell types that underlie the serotonergic modulation of the loudness-dependent response in the primary auditory cortex remain unclear, though previous work has implicated both 5-HT 1A receptors 41 and SERT.…”

Serotonin modulates optimized coding of natural stimuli through increased neural and behavioural responses via enhanced burst firing

“…We predict that these will be most applicable to other systems for which the distribution and functional role of serotonergic feedback is similar to that observed in the electrosensory system, such as the dorsal cochlear nucleus, which is also a cerebellar‐like structure (Felix et al . 2017).…”

Serotonin Selectively Increases Detectability of Motion Stimuli in the Electrosensory System

“…In particular, as the ELL is a cerebellar-like structure, it is likely that our results will be applicable to other cerebellar-like structures such as the dorsal cochlear nucleus (DCN) that also receive large serotonergic innervation. A recent study is shown that serotonin application increases the excitability of DCN neurons via 5-HT2 receptors but had heterogeneous effects on neural responses to stimuli ( Felix et al, 2017 ). We hypothesize that the function of the serotonergic input to DCN will also be to enhance neural responses to stimuli that elicit descending input.…”