[PhD Thesis Presentation] ‐ Mr. Stefan Pommer "The effect of serotonin receptor 5-HT1b on lateral inhibition between spiny projection neurons in the mouse striatum"

Presenter: Mr. Stefan Pommer

Supervisor: Prof. Jeffery Wickens

Unit: Neurobiology Research Unit

Title: The effect of serotonin receptor 5-HT1b on lateral inhibition between spiny projection neurons in the mouse striatum

Anstract:

Striatal spiny projection neurons (SPNs) make inhibitory synaptic connections with each other via collaterals of their main axon, forming a local lateral inhibition network. Previous studies have shown that serotonin, acting via the 5-HT1B receptor, modulates neurotransmitter release from terminals in the target nuclei of SPN projections. Despite this well accepted function, the role of 5-HT1B receptors in lateral inhibition locally among SPNs remains poorly understood. In this thesis, I investigate the role of 5-HT1B in lateral inhibition. To address this issue, whole-cell patch clamp recordings were made from SPNs in acute brain slices, while stimulating presynaptic SPNs expressing Channelrhodopsin. Inhibitory postsynaptic currents (iPSCs) mediated by GABA were measured before and after application of a 5-HT1B receptor agonist. Activation of 5-HT1B receptors significantly reduced the amplitude of iPSCs in SPNs for both, direct and indirect pathways. This was recovered by application of a 5-HT1B antagonist. Further analysis showed the effect was due to a reduced presynaptic release probability of GABA rather than a change in release size. Collectively, these results suggest a prominent role of serotonin in modulating lateral inhibition among striatal neurons and in general striatal function. The 5-HT1b receptor may therefore be a suitable target for future behavioral experiments investigating the currently unknown function of lateral inhibition in the striatum.