Functional network activity and neurotransmitter release
This subproject (SP) will characterize iPS-derived neuronal cultures prepared by SP3 to detect electrophysiological changes by means of a microelectrode array (MEA) system while IPS cells differentiate into neurons. Furthermore, this SP will validate in vivo predictions made by SP7 ex vivo: i) how cellular and synaptic changes in the prefrontal cortex (PFC) of an alcohol-addicted brain lead to changes in network dynamics and ii) how pharmacological treatments reverse altered neurodynamic properties. Rats are either naiv, alcohol-experienced but non-addicted or alcohol-addicted, and are provided by our consortium (SP5). In vivo electrophysiology will measure unit-activity, local field potentials (LFPs) and oscillatory activity, and we will characterize synchronized burst discharges and network oscillatory activity in specific frequency bands. To test predictions made by SP8, in vivo microdialysis and voltammetry will characterize neurotransmitter changes. Together, this SP will lead to the in vivo identification of mechanisms mediating compulsive drinking and relapse behavior at the neurophysiologcal and neurochemical level, and will support the development of novel treatment targets.
Keywords: alcohol addiction, inducible pluripotent stem cells, prefrontal cortex, neurotransmitter, pharmacological treatment