Serotonergic modulation of ventral cochlear nucleus neurons

Serotonergic neurons originating in the dorsal raphe are known to project diffusely the cochlear nucleus. Some serotonergic receptor subtypes (5-HT1A, 5-HT2A, and 5-HT2C) have been shown to be expressed in the neurons, stellate and bushy, of the anteroventral cochlear nucleus (AVCN). In this study, it was aimed to determine the effect of serotonin on the excitability of AVCN neurons and to determine the receptors and ion channels mediating this effect. For this purpose, immunohistochemical studies were performed to test whether the aforementioned receptor types are expressed in AVCN neurons. Further, the modulation of neurons by serotonin and the ionic basis of this modulation were investigated using the electrophysiological patch clamp technique. Electrophysiological studies were conducted on mice aged 14-17 days and immunohistochemical studies were conducted on 30-35-day-old BALB/c mice. In immunohistochemical studies, 5-HT1A and 5-HT2A receptors were labeled more intensely than 5-HT2C receptors. In electrophysiological studies, serotonin depolarized stellate and bushy cells by 4.93 mV and 5.78 mV, respectively. Serotonin statistically increased the number of action potentials in stellate cells (n=11, p<0.005). The antagonists of 5-HT1A, 5-HT2A and 5-HT2C serotonin receptors, WAY 100635 (10 µM), 4F 4PP oxalate (1 µM ) and SB 242084 (10 µM), respectively, reduced the depolarization caused by serotonin in both cell types to varying degrees. The depolarizing effect of serotonin was mediated through HCN channels. As a result of serotonin application, it was determined that the half-activation voltage value shifted in the positive direction (right) by 2.4 mV and 3.1 mV in stellate and bushy neurons, respectively. Electrophysiologically, we showed that the Ih current of serotonin caused modulation of passive and active membrane properties of these neurons by shifting the steady-state activation curve of HCN channels in the direction of depolarization.