Serotonergic Regulation of Excitability of Principal Cells of the Dorsal Cochlear Nucleus

http://www.jneurosci.org/content/35/11/4540.abstract

The dorsal cochlear nucleus (DCN) is one of the first stations within the central auditory pathway where the basic computations underlying sound localization are initiated and heightened activity in the DCN may underlie central tinnitus. The neurotransmitter serotonin (5-hydroxytryptamine; 5-HT), is associated with many distinct behavioral or cognitive states, and serotonergic fibers are concentrated in the DCN. However, it remains unclear what is the function of this dense input. Using a combination of in vitro electrophysiology and optogenetics in mouse brain slices, we found that 5-HT directly enhances the excitability of fusiform principal cells via activation of two distinct 5-HT receptor subfamilies, 5-HT2A/2CR (5-HT2A/2C receptor) and 5-HT7R (5-HT7 receptor). This excitatory effect results from an augmentation of hyperpolarization-activated cyclic nucleotide-gated channels (Ih or HCN channels). The serotonergic regulation of excitability is G-protein-dependent and involves cAMP and Src kinase signaling pathways. Moreover, optogenetic activation of serotonergic axon terminals increased excitability of fusiform cells. Our findings reveal that 5-HT exerts a potent influence on fusiform cells by altering their intrinsic properties, which may enhance the sensitivity of the DCN to sensory input.

 

Ok, someone translate please!

 

Benyru mentioned serotonin depletion was linked to potassium channel closure.

 

Yeah, that could explain why some doctor cured a patient's hyperacusis with Fluoxetine. That's a serotonin reuptake inhibitor that opens block on Kv3.1 potassium channel. But on the other hand I'm sure that one is also reported ototoxic somewhere. Sigh.

 

sounds like in a few years they will be able to fix tinnitus with optogenetics. Meaning, they inject you with a synthetic retrovirus which permanently rewrites the DNA of DCN cells to include a photoresponsive protein, and then when your ear ringing pisses you off, you shine a blue light over the back of your head and it all quiets down...